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RC646  .C67  Pri^iafy  neoplasms  ot 


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PRIMARY  NEOPLASMS  OF  THE 
LYMPHATIC  GLANDS 

INCLUDING  HODGKIN'S  DISEASE 


By  WILLIAM  B.  COLEY,  M.D. 

NEW  YORK 


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in  2010  with  funding  from 

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http://www.archive.org/details/primaryneoplasmsOOcole 


PRIMARY  NEOPLASMS  OF  THE 
LYMPHATIC  GLANDS 

INCLUDING  HODGKIN'S  DISEASE 


BY 

WILLIAM  B.  COLEY,  M.D. 

NEW  YORK 


Reprinted  from 

The  Transactions  oj  the  American  Surgical  Association 

1915 


CONTENTS 


Diagnosis 4 

Treatment 6 

Hodgkin's  Disease 8 

Sarcoma  of  the  Neck 15 

Sarcoma  of  Tonsil  and  Neck 31 

Sarcoma  of  Axillary  Glands 46 

Sarcoma  of  Inguinal  Glands 53 

Sarcoma  of  Retroperitoneal  and  Mesenteric  Glands        ...  56 

Sarcoma  of  Mediastinal  Glands 62 

Borderline  Cases  with  Clinical  Diagnosis  of  Hodgkin's  Disease, 

Microscopic  Diagnosis  of  Sarcoma,  or  Vice  Versa  ...  63 
Rare  Types   of   Malignant   Disease   of  the   Lymphatic  Glands: 

(a)  Melanoma;  (&)  Carcinoma 82 

Cases  of  Sarcoma  of  Lymphatic  Glands  Successfully  Treated  by 

other  Surgeons  with  the  Mixed  Toxins  (Coley)    ....  112 

Summary  of  Results 116 -118 

Recurrence  after  Apparent  Cure 119 

Tables ■ 122-146 


PRIMARY  NEOPLASMS  OF  THE  LYMPHATIC  GLANDS 
INCLUDING  HODGKIN'S  DISEASE 


By  WILLIAM  B.  COLEY,  M.D. 

NEW   YORK 


This  paper  is  an  attempt  to  add  some  further  clinical  data 
bearing  upon  primary  tumors  of  the  lymphatic  glands,  on  the 
basis  of  a  study  of  i68  cases  personally  observed. 

I  scarcely  need  state  that  this  group  of  neoplasms  gives  the 
most  hopeless  prognosis  of  any  in  the  entire  field  of  malignant 
tumors — hopeless  not  only  from  the  stand-point  of  surgery,  but 
also  as  regards  x-ray  and  radium  treatment. 

I  should  like  to  discuss  the  clinical  diagnosis  of  neoplasms  of 
the  lymphatic  glands  if  time  and  space  permitted.  I  can  merely 
say  that  while  in  many  cases  it  is  possible  to  make  a  correct 
diagnosis  from  clinical  signs  alone,  together  with  the  history  of 
the  case,  rapidity  of  growth,  and  blood  examinations;  in  most 
cases  a  positive  early  diagnosis  cannot  be  made  without  a  micro- 
scropic  examination,  and  not  always  then.  I  do  not  believe 
there  is  much  risk  in  an  exploratory  operation  for  the  removal 
of  enough  tissue  for  a  microscopic  examination.  In  many  of 
these  cases  the  tumor  is  made  up  of  a  considerable  number  of 
more  or  less  discrete  glands,  and  one  small  gland  can  be  taken 
out  with  little  risk  of  producing  generalization  of  the  disease. 

The  almost  hopeless  prognosis  of  the  disease  has  been  empha- 
sized by  the  paper  of  Fabian^  based  upon  the  results  of  treat- 
ment in  a  large  series  of  cases  collected  by  him.  "Operation," 
he  emphatically  declares,   "can  come  into  consideration  only 

1  Miinchener  med.  Wochenschr. ,  August  26,  1913,  No.  34,  p.  1876. 


2       COLEY:  NEOPLASMS  OF  THE  LYMPHATIC  GLANDS 

in  such  cases  in  which  the  site  of  the  disease  is  isolated,  a  thing 
which  it  is  often  difficult  to  prove.  It  is  furthermore  necessary 
to  exclude  leukemia  and  pseudoleukemia  by  quantitative  and 
and  qualitative  blood  analysis,  tuberculosis  by  Pirquet's  and 
lues  by  a  Wassermann  reaction."  He  further  holds  that,  in 
^'iew  of  the  extreme  difficulty  in  making  an  early  definite  diagno- 
sis, it  is  essential  to  do  an  exploratory  incision  for  the  purpose 
of  microscopic  examination  which  in  the  majority  of  cases 
enables  one  to  differentiate  between  lymphosarcoma  and  Hodg- 
kin's  disease.  "Clinically,"  he  states,  "these  two  conditions 
ma}'  be  deceptively  similar,  a  circumstance  which  would  not  be 
of  great  importance  were  the  treatment  of  the  two  lesions  the 
same.  This,  however,  is  not  the  case.  Operation,  according  to 
.our  present  knowledge,  is  contra-indicated  in  cases  of  malignant 
lymphoma  even  if  localized  in  character.  Numerous  observa- 
tions ha\dng  shown  that  in  these  cases,  as  in  leukemia  and 
pseudoleukemia,  the  most  thorough  excision  often  does  not 
check  the  progress  of  the  disease,  but,  on  the  contrary,  causes 
more  rapid  proliferation." 

"On  the  basis  of  the  collected  experience  up  to  the  present 
time,"  Fabian  states,  "we  must  admit  that  surgical  treatment 
in  general  has  been  most  discouraging."  He  cites  the  exhaustive 
compilation  of  Dufhus.  in  1895,  comprising  22  cases  of  lympho- 
sarcoma of  the  neck  and  axilla  observed  at  the  Greifswald  Clinic. 
Of  these  3  were  inoperable;  3  of  the  remaining  19  were  operated 
upon  by  exploratory  incision  only;  6  of  the  cases  treated  by 
radical  operation  had  a  speedy  recurrence;  g  left  the  cKnic  well 
but  in  4  of  these  a  recurrence  was  soon  observed;  i  patient  was 
operated  upon  four  times.    No  permanent  cures  are  mentioned. 

The  number  of  cases  in  which  the  appearance  of  the  sar- 
coma in  the  cer^dcal  glands  is  preceded  by  an  attack  of 
tonsillitis  or  sore  throat,  points  very  strongly  to  an  infectious 
origin.  One  of  the  cases  in  my  series,  which  I  have  given  in  some 
detail,  also  points  very  strongly  toward  an  extrinsic  and  infec- 
"  tious  origin  other  than  through  the  tonsil.  In  this  case  the  patient 
cut  her  finger  on  a  vase;    a  swelling  in  the  axillary  gland  on  the 


coley:  neoplasms  of  the  lymphatic  glands  3 

same  side  almost  immediately  appeared  and  developed  into  a 
rapidly  growing  sarcoma.  Of  course,  in  this  case  it  is  not  pos- 
sible to  prove  tbe  causative  connection  between  the  prick  of 
the  finger  and  the  sarcoma;  the  latter  may  have  been  merely 
a  coincidence,  still  in  connection  with  the  cervical  cases  following 
an  infection  in  the  tonsil  it  is  certainly  suggestive. 

There  is  much  evidence  pointing  to  a  very  close  relationship 
between  the  groups  of  tumors  at  present  designated  as  mahg- 


FiG.   I. — Hodgkin's  disease. 

nant  tumors — sarcoma  and  carcinoma — and  the  group  regarded 
as  Hodgkin's  disease.  Indirect  evidence  of  this  close  relationship 
is  suggested  by  the  recently  published  experimental  work  of  Dr. 
Maude  Slye,  of  Chicago,  covering  a  period  of  ten  years.  She 
found  that  cancer  was  apparently  hereditary  in  mice,  and  was  able 
to  produce  a  breed  of  mice  in  which  practically  every  member 
of  the  family  died  of  cancer. 
Aside  from  the  question  of  heredity — -which  is  irrelevant  to 


4  coley:  neoplasms  of  the  lymphatic  glands 

the  topic  under  discussion — she  found  that  all  the  different 
types  of  malignant  disease  were  produced  in  these  cancer  families, 
one  having  carcinoma,  another  sarcoma,  another  epithelioma, 
I  and  still  others  Hodgkin's  disease  and  lymphatic  leukemia. 
Furthermore,  these  latter  conditions  she  has  never  observed 
except  in  cancer  families. 

To  turn  for  the  moment  to  the  histological  features  in  these 
different  tumors  of  the  lymphatic  glands,  we  find  there  is  great 
difference  of  opinion  in  characterizing  the  histological  structures. 

In  one  of  my  cases,  a  tumor  of  the  axillary  glands  was  pro- 
nounced, in  the  original  report,  lymphosarcoma,  and  the  same 
pathologist  two  years  later  described  it  as  an  endothehoma. 
Other  specimens  were  pronounced  round-celled  sarcoma  by  one 
pathologist  and  Hodgkin's  disease  by  another.  This  is  a  com- 
mon observation.  Not  infrequently  have  I  received  the  following 
opinion : 

''The  tumor  is  certainly  malignant,  but  whether  sarcoma,  or 
carcinoma,  I  am  uncertain."  The  term  "embryonal  carci- 
noma," much  used  of  late,  is  being  more  and  more  frequently 
employed  to  describe  some  of  these  border-line  cases.  Herein 
lies  the  great  significance  of  the  study  of  primary  neoplasms  of 
the  lymphatic  glands.  This  study  leads  one  to  pay  less  and 
less  heed  to  the  finer  histological  distinctions,  the  ''judicial 
niceties"  of  the  microscopic  examination  in  these  cases — the 
interpretation  of  which  is  by  no  means  clear — but  rather  to 
group  the  cases  according  to  certain  well-defined  clinical  fea- 
tures. Thus  we  have  a  group  of  the  so-called  Hodgkin's  type 
of  tumors,  or  neoplasms  of  the  lymphatic  glands,  with  fairly 
distinct  clinical  features,  sufficiently  characteristic  in  the  ordi- 
nary case  to  make  the  diagnosis  comparatively  easy,  namely: 

I.  Enlarged  glands,  usually  beginning  (in  the  cervical  region) 
on  the  one  side,  and  soon  involving  those  on  the  other  side; 
freely  movable;  more  or  less  discrete,  skin  not  attached;  mod- 
erately firm  in  consistence  but  not  fluctuating,  gradually  followed 
by  involvement  of  the  axillary  a^d  inguinal  glands,  and  not 
infrequently  the  spleen  and  liver;    a  blood  picture  which  Bunt- 


coley:  neoplasms  of  the  lymphatic  glands  5 

ing  and  Yates  believe  to  be  peculiarly  characteristic :  a  more  or  less 
rapid  deterioration  in  general  health,  uniformly  endingin  death. 
2.  The  ordinary  type  of  round-celled  sarcoma  of  the  cervical 
glands,  beginning  as  a  single  nodule,  softer  in  consistence  and 
more  apt  to  infiltrate  the  surrounding  tissue  than  in  the  Hodg- 
kin's  type;  may  extend  to  the  glands  on  the  opposite  side,  but 
this  is  not  usual  in  the  early  stages;   more  rapid  increase  in  size; 


Fig.  2. — Lymphosarcoma. 

more  frequently  associated  with  pain;  running  a  much  more 
rapid  course  than  the  ordinary  Hodgkin's  and  only  infrequently 
causing  general  metastasis.  It  resembles  Hodgkin's  in  the  fatal 
prognosis.  The  differential  diagnosis  of  this  type  of  tumor  from 
tuberculosis  is  not  usually  difficult,  owing  to  its  very  rapid 
progress  without  any  tendency  to  become  caseous. 

Then  we  have  a  third  group  of  cases  designated  ordinarily  as 
lymphatic  leukemia,  which  differs  from  the  Hodgkin's  very  httle 
except  in  the  blood  picture.     I  beheve  it  is  possible  to  regard 


6  coley:  neoplasms  of  the  lymphatic  glands 

this  group  of  cases  as  closely  allied  to  Hodgkin's,  and  perhaps  a 
different  stage  of  the  same  disease.  A  uniformly  hopeless  prog- 
nosis is  common  to  each  of  these  different  groups. 

the  treatment  of  primary  sarcoma  of  the  lymphatic 

GLANDS 

If  the  disease  is  discovered  before  more  than  a  single  gland 
has  become  involved  it  should  be  removed  by  surgical  operation 


Fig.  3. — Lymphosarcoma  of  tonsil. 

and  the  patient  put  upon  a  prolonged  course  of  treatment  with 
the  mixed  toxins  of  erysipelas  and  Bacillus  prodigiosus,  in  the 
hope  of  preventing  a  recurrence. 

If  the  disease  is  primary  in  the  tonsil,  and  is  discovered  before 
the  surrounding  tissues  have  become  markedly  infiltrated,  and 
before  metastases  have  taken  place  in  the  glands  of  the  neck,  ■ 
the  tonsil  should  be  removed,  and  if  the  diagnosis  is  confirmed 
by  microscopic  examination,  similar  prophylactic  toxin  treatment 
should  be  instituted. 


coley:  neoplasms  of  the  lymphatic  glands  7 

One  of  the  most  remarkable  cases  of  an.  apparent  cure  is  that 
in  which  a  large  tumor,  a  round-celled  sarcoma,  of  the  tonsil 
and  cervical  glands  disappeared  under  seven  weeks'  treatment 
with  the  mixed  toxins  of  erysipelas  and  Bacillus  prodigiosus 
and  the  patient  remained  well  for  nearly  seven  years,  when  a 
similar  trouble  developed  in  the  opposite  tonsil  and  neck,  and 
rapidly  recurred  after  two  operations.  Following  the  recur- 
rence after  the  second  operation  the  mixed  toxins  were  used  for 


Fig.  4. — Hodgkin's  disease;  rapid  course. 

a  short  time  with  apparently  little  effect.  The  patient  died 
two  months  later.  Here  it  is  fair  to  believe  that  the  original 
tumor  was  completely  cured  and  that  the  one  in  the  opposite 
side  was  an  entirely  new  development,  not  a  recurrence  of  the 
original  tumor. 

In  many  cases  it  is  almost  certain  that  operation,  particularly 
incomplete  operation,  greatly  increases  the  malignancy  of  the 
tumor  and  causes  it  to  grow  more  rapidly  than  before.    Hence^ 


8  coley:  neoplasms  or  the  lymphatic  glands 

I  believe  that  "palliative  operations,"  or  partial  operations,  in 
this  class  of  cases  are  contra-indicated. 

In  view  of  the  importance  of  establishing  the  correctness  of 
the  diagnosis,  beyond  question,  I  believe  that  a  portion  of  tissue, 
preferably  a-  small  isolated  gland,  sufficiently  large  to  permit 
of  microscopic  examination,  should  be  removed;  this  can  be 
done  in  most  cases  without  any  material  risk  in  the  way  of  caus- 
ing metastasis  or  increasing  the  malignancy  of  the  growth. 

The  prognosis  after  x-ray  treatment  in  these  cases  is  not 
infrequently  good  as  regards  immediate  result;  but  as  Fabian 
states,  and  my  own  experience  confirms,  there  have  been  no 
permanent  cures  from  the  x-rays  in  this  group  of  cases.  The 
same  is  true  of  radium. 

hodgkin's  disease 

Assuming  the  correctness  of  the  view  which  I  have  long  held 
that  Hodgkin's  disease  is  a  type  of  sarcoma,  closely  related, 
etiologically,  I  believe  the  same  treatment  should  be  applied  to 
Hodgkin's  disease  as  to  sarcoma  of  the  lymphatic  glands. 

If  the  disease  is  discovered  in  the  early  stages,  when  only 
one  or  a  few  glands  are  involved,  most  extensive  and  radical 
removal,  if  possible,  should  be  employed,  always  accompanied 
by  enucleation  of  the  tonsils,  if  enlarged,  as  they  are  the  most 
probable  source  of  primary  infection. 

Inasmuch  as  operation  alone  is  practically  always  followed  by 
a  recurrence  of  the  disease,  any  hope  of  a  cure  must  depend  upon 
postoperative  treatment. 

Yates  and  Bunting  believe  that  long-continued  x-ray  treat- 
ment together  with  enucleation  of  the  tonsil  has  apparently 
effected  a  cure  in  two  cases,  the  patients  having  remained  well 
upward  of  five  years. 

It  should  be  noted  that  in  both  of  these  cases  the  disease  was 
attacked  while  in  the  very  early  stages,  both  having  been  sons 
of  physicians,  and  the  disease  was  recognized  comparatively 
early. 


coley:  neoplasms  of  the  lymphatic  glands  9 

In  one  case,  first  treated  in  November,  1908,  diagnosis  con- 
firmed by  microscopic  diagnosis,  tonsillectomy  was  followed 
by  x-ray  treatment  and  hygienic  measures.  In  this  case  there 
were  only  a  few  enlarged  bilateral  cervical  and  axillary  glands, 
with  no  involvement  of  abdominal  glands,  spleen,  or  liver.  In 
December,  191 2,  a  few  glands,  smaller  than  peas,  could  be 
felt  in  the  posterior  triangle  of  the  neck,  but  none  in  the  groin. 


Fig.  5. — Clinical  diagnosis  was  sarcoma  of  neck.    Microscopic  diagnosis  was 

Hodgkin's  disease. 

In  January,  1914,  six  years  after  the  beginning  of  the  treatment, 
the  patient  was  in  excellent  health;  the  blood  picture  was 
negative. 

In  the  other  case  of  Yates  and  Bunting,  ten  years  of  age,  there 
was  slight  enlargement  of  the  glands  in  the  axillae  and  groins; 
abdomen  negative;  blood  picture  positive  Hodgkin's;  axillary 
gland  removed  for  diagnosis;  pronounced  Hodgkin's.  In  this 
case  the  disease  was  first  noticed  in  December,   1909;     1910. 


lo  coley:  neoplasms  of  the  lymphatic  glands 

tonsillectomy,  followed  by  x-yslj  and  hygienic  treatment.  Sep- 
tember, 1913:  glandular  condition  about  the  same;  a  few 
slightly  enlarged  glands  palpable.  January  6,  1914:  blood 
picture  normal;  glands  quiescent.  This  patient  was  well  at 
the  last  observation,  made  four  years  after  the  beginning  of  the 
treatment. 

Nearly  everyone  has  observed  very  marked  beneficial  effects 
following  the  use  of  the  x-rays  in  Hodgkin's  disease  in  almost  all 


Fig.  6. — Lymphosarcoma. 

its  stages;  but  aside  from  the  cases  observed  by  Bunting  and 
Yates,  I  believe  there  is  not  a  single  case  on  record  of  a  cure 
by  this  agent;  nor  do  I  consider  it  proper  to  regard  the  two 
cases  cited  in  their  series  as  positive  cures.  It  should  be  noted 
that  in  both  of  these  cases  they  were  dealing  with  in  an  early 
stage  of  the  disease,  and  there  was  no  evidence  of  involvement 
of  the  spleen  or  liver,  such  as  was  present  in  my  cases  treated 
with  the  toxins. 


coley:  neoplasms  of  the  lymphatic  glands 


II 


My  reasons  for  advocating  the  toxins  in  Hodgkin's  disease  are 
based  upon  the  remarkable  effects  that  I  have  observed  in  a 
number  of  such  cases,  particularly  the  two  in  which  entire 
disappearance  of  the  lesions  occurred. 

The  following  two  cases  of  Hodgkin's  disease  have  been 
reported  somewhat  fully  in  my  earlier  papers: 


Fig.  7.— Case  I.  Hodgkin's  disease.  Entire  disappearance  of  tumors 
in  neck,  oxilla,  and  groin.  Return  of  liver  and  spleen  to  normal  size.  Under 
six  weeks  mixed  toxins  alone.     Recurred  in  six  months.     Death  in  one  year. 


Case  I.^ — Hodgkin's  disease:  Clinical  diagnosis  confirmed  by 
microscopic  examination;  entire  disappearance  of  lymphatic  and 
splenic  enlargement  under  two  months''  treatment  with  mixed  toxins 
of  erysipelas  and  Bacillus  prodigiosus,  without  other  treatment. 

G.  K.,  aged  twenty- four  years;    family  history  negative. 

This  patient  felt  so  entirely  well  that  he  refused  any  further 

1  Further  Evidence  in  Support  of  the  Theory  that  Hodgkin's  Disease  is  a 
Type  of  Sarcoma,  Transactions  of  the  American  Surg.  Assn.,  1908. 


12 


coley:  neoplasms  of  the  lymphatic  glands 


treatment,  and  left  the  hospital.  He  gained  forty  pounds  in 
weight  and  remained  in  good  condition  for  about  seven  months. 
Shortly  after,  all  of  his  former  symptoms  returned,  and  the 
disease  progressed  rapidly,  causing  death  in  about  six  months; 
this  proves  the  correctness  of  the  diagnosis. 

The  second  case^  I  believe  to  be  so  remarkable  that  I  have 
decided  to  reproduce  it  in  full. 


Fig.  8. — Hodgkin's  disease. 


Fig.  9. — Lymphosarcoma  of  the 
neck.  About  thirty  x-ray  exposures 
before  entering  the  hospital;  no  effect. 
Few  treatments  were  given  in  hospital. 


Case  II. — Advanced  Hodgkin's  disease  successfully  treated  with 
the  mixed  toxins  of  erysipelas  and  Bacillus  prodigiosus. 

The  patient  was  treated,  under  my  direction,  by  Dr.  C.  E. 
Preston,  of  Ottawa,  Canada,  one  of  my  former  house  surgeons. 

G.  M.,  aged  nineteen  years,  was  admitted  to  the  Ottawa  Hos- 
pital May  4,  1908,  with  a  history  of  glandular  sweUing  beginning 
on  one  side  of  the  neck  and  later  involving  both  sides,  of  about 
one  year's  duration.  There  was  gradual  loss  of  weight  and 
increasing  anemia.    The  glands  of  the  neck  were  greatly  enlarged; 

1  A  Report  of  Recent  Cases  of  Inoperable  Sarcoma  Treated  with  Mixed 
Toxins  of  Erysipelas  and  Bacillus  Prodigiosus,  Cancer  Research  Society, 
Buffalo,  April  12,  1922,  and  Surgery,  Gynecology  and  Obstetrics,  August, 
1911. 


coley:  neoplasms  of  the  lymphatic  glands 


13 


the  spleen  was  enlarged  and  palpable  three-fourths  of  an  inch 
below  the  margin  of  the  ribs;  the  liver  extended  three  inches 
below  the  border  of  the  ribs;  inguinal  glands  were  moderately 
enlarged.  Weight,  122  pounds.  The  diagnosis  of  Hodgkin's 
disease  was  made  by  all  of  the  attending  physicians  and  surgeons 
of  the  hospital  and  a  hopeless  prognosis  was  given. 

The  mixed  toxins  were  begun  June  i,  the  initial  dose  being 
one-fourth  minim.  This  was  gradually  increased  until  July 
July  10,  the  maximum  dose  of  twelve  minims  was  reached. 
This  caused  a  temperature  of  103°  and  a  rather  severe  chill. 


Fig.  10. — -Round- celled  sarcoma 
of  neck.  Decreased  three-quarters 
in  one  week,  but  later  increased. 
Patient  died  four  months  later. 


Fig.  II.— Round-celled  sarcoma. 


The  treatment  was  continued  for  three  months,  partly  by  the 
family  physician.  Examination  on  January  i,  1909,  showed 
the  patient  quite  well,  weight  145  pounds,  with  only  a  small 
gland  in  the  right  side  of  the  neck.  He  had  returned  to  his  usual 
work.    The  toxins  were  discontinued. 

Reexamination  on  September  10,  1909,  by  the  family  physi- 
cian shows  the  patient  in  fine  condition,  all  the  glands  have  dis- 
appeared and  he  continues  his  hard  work.  Under  date  of  April 
6,  191 1,  Dr.  Preston  stated  that  he  had  just  examined  the  patient 
and  found  him  in  perfect  condition. 


14 


coley:  neoplasms  of  the  lymphatic  glands 


Under  date  of  September  i,  1915,  Dr.  R.  E.  Webster,  of  the 
County  Carleton  Genera]  Hospital  (Ottawa,  Canada),  writes 
that  the  patient  at  present  is  in  perfect  health  seven  years  later. 
Glandular  system  is  apparently  normal.  He  further  adds  that, 
while  no  glands  were  removed,  the  case  was  a  typical  one  of 
Hodgkin's  disease;  all  the  glandular  symptoms  were  present. 
The  patient  was  treated  from  June  i  to  July  30  at  the  Ottowa 
Hospital,  after,  1908,  which  the  toxin  treatment  was  carried  on 
by  the  family  physician  at  home. 


Fig.   12. — Pathological  diagnosis  was  sarcoma,  but  clinical  course  was  that 
of  Hodgkin's  disease. 


In  spite  of  the  absence  of  a  microscopic  examination  there 
can  be  little  doubt  that  the  diagnosis  of  Hodgkin's  disease  was 
correct. 

All  evidence  of  the  disease  disappeared  under  no  other  treat- 
ment than  the  toxins,  and  the  patient  has  remained  well  for 
more  than  seven  years  after  treatment.  I  believe  this  case 
comes  nearer  to  being  a  permanent  cure  than  any  case  thus 
far  recorded. 

The  more  important  cases  of  my  series  are  given  in  consider- 
able detail,  the  entire  number  being  reported  in  tabular  form 
at  the  end  of  this  paper.    Some  of  the  cases  have  been  previously 


coley:  neoplasms  of  the  lymphatic  glands  15 

reported  in  the  Transactions  of  the  Third  International  Cancer 
Research  Conference  (Brussels,  1913),  but  inasmuch  as  this 
volume  is  likely  to  be  found  only  in  the  larger  Hbraries,  and  in 
order  to  make  the  paper  complete,  I  have  thought  it  wise  to  re- 
produce the  histories  of  these  cases  either  in  full  or  in  abstract, 
the  most  important  feature  being  the  addition  of  full  data  as  to 
the  subsequent  progress  in  the  cases  that  are  still  living. 


Fig.   13. — Hodgkin's  disease 
I.    SARCOMA    OF    THE    NECK 

Case  III. — Round-celled  lymphosarcoma  of  the  neck  and  supra- 
clavicular glands  recurrent;  inoperable. 

A.  P.,  female,  aged  two  years  and  ten  months.  Referred  to  me 
by  Dr.  E.  J.  McKnight,  of  Hartford,  Conn.,  in  March,  1902.  Pri- 
mary tumor  removed  by  Dr.  McKnight  at  the  Hartford  Hospital 
on  January  27,  1902.  No  examination  of  the  specimen  was  made, 
but  the  tumor  rapidly  recurred  and  a  second  operation  was  done 
in  March,  1902.  The  specimen  removed  at  this  time  was  exam- 
ined by  Dr.  W.  R.  Steiner,  pathologist  at  the  Hartford  Hospital, 
who  made  the  diagnosis  of  smaH  round-celled  sarcoma.  The 
disease  was  considered  too  extensive  for  removal.  The  patient 
was  first  seen  by  me  on  March  8,  191 2,  when  I  found  a  series  of 
tumors  extending  from  the  clavicle  to  the  mastoid  bone  on  the 
right  side;  the  submaxillary  and  axillary  glands  on  the  right 
side  were  also  involved;    the  cKnical  appearance  of  the  disease 


i6 


coley:  neoplasms  oe  the  lymphatic  glands 


was  typically  sarcomatous.  I  advised  the  toxin  treatment  which 
was  carried  out  by  Dr.  McKnight  for  about  three  months. 
Immediate  improvement,  followed  by  complete  disappearance. 


Fig.   14. — Round-celled  sarcoma  of  neck 


/ 


Fig.   15. — Hodgkin's  disease. 


Fig.   16. — Round-celled  sarcoma  of 
neck. 


In  a  letter  dated  June  9,  191 5,  the  patient  states  that  she  is 
well  at  present,  over  thirteen  years  afterward. 

This  patient  was  also  shown  before  the  Congress  of  Clinical 
Surgeons  of  North  America  on  November  12,  191 2,  and  before 
the  Internationa]  Congress  of  Surgery,  April  12,  19 14. 


coley:  neoplasms  of  the  lymphatic  glands 


17 


Case  IV. — Round-celled  sarcoma  of  the  neck. 

F.  W.,  male,  aged  fifty-eight  years  of  age,  referred  to  me 
by  G.  H.  Gray,  of  Lynn,  Massachusetts,  December  21,  1908. 
Family  history  negative.  Personal  history:  Two  years  before 
patient  noticed  a  small  painless  tumor  in  the  right  cervical 
region.  This  grew  slowly  at  first,  but  more  rapidly  later,  and  at 
the  time  of  the  first  operation,  November  24,  1908,  by  Dr. 
Gray,  the  tumor  had  reached  the  size  of  a  small  egg.  It  was 
found  impossible  to  make  a  complete  removal.  At  the  time 
the  patient  came  to  me  (December  21,  1908,  there  was  a  well- 


FiG.  17. 


-Round-celled  sarcoma  of 
neck. 


Fig.  18. — Round-celled  sarcoma  of  the 
neck  after  one-third  disappearance. 


marked  recurrence,  and  the  condition  was  inoperable.  The 
patient  was  admitted  to  the  general  Memorial  Hospital  on  the 
25th  of  December,  1908,  and  received  eleven  treatments  under 
my  care.  He  was  then  advised  to  return  to  his  home,  and  the 
treatments  were  continued  by  Dr.  Gray.  He  had  82  injections 
altogether,  the  highest  dose  being  5  and  4.5  minims;  the  tem- 
perature ranging  between  99.5°  and  100°.  At  the  end  of  six 
months  the  toxins  were  given  but  once  a  week.  The  treatment 
was  continued  for  nearly  a  year  altogether.  Examination, 
November    11,    1909,   nearly   a  year   after   the   treatment  was 


i8  coley:  neoplasms  or  the  lymphatic  glands 

begun,  showed  a  three-inch  cicatrix  over  the  interior  sterno 
mastoid  region,  soft,  pHable,  with  no  evidence  of  a  tumor  remain- 
ing. General  health  was  perfect.  In  a  letter  received  from  Dr. 
Gray  (dated  April  9,  191 1)  he  states  that  the  patient  is  well  at 
present  and  in  perfect  general  health,  nearly  two  and  one-half 
years  later.  October  9,  1913,  Dr.  Gray  writes:  "M.  W.  is  alive 
and  we]]."  He  remains  well  June,  1915,  six  and  a  half  years 
later. 


Fig.  19. — Case  IV.  Inoperable  recurrent  sarcoma  of  neck.  Entire  dis- 
appearance under  toxin  treatment.  Patient  well  at  present,  over  three  years 
later. 

Case  V. — Small  round-celled  sarcoma  of  the  neck.  Entire  dis- 
appearance under  three  months^  treatment  with  the  mixed  toxin. 
Patient  well  at  present,  six  years  later. 

P.  K.,  male,  aged  forty-one  years,  heavy  smoker.  First 
noticed  a  lump  in  the  submaxillary  region  in  April,  1909.  This 
grew  rapidly,  and  by  June  had  reached  the  size  of  a  hen's  egg. 


coley:  neoplasms  of  the  lymphatic  glands  19 

On  June  11,  1909,  the  patient  was  admitted  to  the  Roosevelt 
Hospital  to  the  service  of  Dr.  Charles  H.  Peck,  who  stated  that 
he  found  a  very  vascular  tumor  which  had  invaded  the  periosteum 
of  the  lower  jaw.  There  was  also  marked  infiltration  of  the 
muscles  and  skin. 

Dr.  Peck  could  not  make  a  complete  removal,  and  gave  a  hope- 
less prognosis.     A  microscopic  examination  was  made  by  Dr. 


Fig.  20. — Melanotic  sarcoma  of  neck  (apparently  primary  in  glands). 

Hodenpyl,  the  pathologist  to  the  hospital,  and  he  pronounced  it 
a  small,  round-celled  sarcoma,  highly  malignant. 

The  patient  was  referred  to  me  by  Dr.  Peck  a  few  weeks  after 
operation,  for  the  toxin  treatment,  which  was  carried  oiit  under 
my  direction  by  Dr.  Lipset,  the  family  physician. 

Shortly  after  the  treatment  was  begun,  the  infiltrated  area 
in  the  region  of  the  cicatrix  began  to  soften  and  recede,  and  at 
the  end  of  three  months  it  had  entirely  disappeared.  The 
toxin  was  kept  up  in  small  doses,  with  intervals  of  rest,  for  one 
year. 


20  coley:  neoplasms  of  the  lymphatic  glands 

The  patient  was  shown  before  the  Congress  of  the  Inter- 
national Surgical  Association,  New  York,  April,  1914,  also 
before  the  Clinical  conference  at  the  General  Memorial  Hospital 
in  March,  1915.  He  remains  in  good  health  without  any  trace 
of  the  disease,  in  July,  191 5,  six  years  afterward. 


Fig.  21. — Hodgkin's  disease. 

Case  VI. — Sarcoma  of  neck. 

E.  M.,  female,  aged  sixty  years,  referred  to  me  by  Dr.  R.  P. 
Sullivan,  of  Brooklyn,  on  May  13,  191 5,  with  the  following 
history : 

Six  months  ago  she  first  noticed  a  4ump  in  the  right  side  of 
the  neck  just  behind  the  angle  of  the  jaw.  This  slowly  increased 
in  size  and  by  the  end  of  April  apparently  involved  the  lower 
portion  of  the  parotid.  The  glandular  tumor  below  the  jaw  was 
removed  on  May  i  at  St.  Mary's  Hospital;  Brooklyn,  and 
microscopic  examination  by  the  pathologist  of  the  hospital 
showed  it  to  be  a  spindle-celled  sarcoma. 

Physical  examination  on  May  13,  1915,  showed  a  recent 
cicatrix,  two  inches  long,  just  below  the  ear,  and  running  along 
the  margin  of  the  jaw.  There  is  some  fulness  or  induration  in 
the  region  of  the  cicatrix,  as  also  a  mass  in  the  region  of  the 
right  parotid  gland,  extending  down  into  the  neck  itself.  The 
tumor  is  firmly  fixed.  The  patient  entered  the  General  Memo- 
rial Hospital  and  was  immediately  put  upon  the  mixed  toxins  of 
erysipelas  and  Bacillus  prodigiosus,  without  other  treatment. 


COLEY:  neoplasms  of  the  lymphatic  glands       21 

She  remained  at  the  Hospital  for  three  weeks  receiving  the 
toxins  in  gradually  increasing  doses  from  0.5  to  6  minims;  dur- 
ing this  time  she  had  five  chills.  The  tumor  slowly  decreased 
in  size  and  at  the  end  of  three  weeks  had  apparently  entirely 
disappeared.  The  toxins  have  been  continued  up  to  the  present 
time,  two  to  three  times  a  week. 

August  20,  1915.     There  is  no  evidence  of  any  return  of  the 
disease. 


Fig.  22,  Case  VII. — Recurrent  sarcoma  of  glands  of  the  neck;  inoperable. 
Disappeared  after  use  of  toxins;  well  two  and  a  half  years  (April,  1915).  Clinical 
diagnosis:  microscopic  doubtful  (very  poor  section). 


Case  VII. — Round-celled  sarcoma  of  the  neck. 

Dr.  P.  V.  In  the  early  part  of  1913,  patient  noticed  a  swelling 
in  the  neck,  starting  midway  between  the  chin  and  thyroid; 
considered  at  first  an  inflammatory  process  by  one,  phlegmon  by 
another  physician.  Operation  by  Dr.  Russell  S.  Fowler,  of 
Brooklyn,  and  after  microscopic  examination  the  disease  was 


22  coley:  neoplasms  of  the  lymphatic  glands 

pronounced  infective  granuloma.  Later  it  was  pronounced 
round-celled  sarcoma.  Three  sections  were  also  submitted  to 
Dr.  William  H.  Welch,  of  Johns  Hopkins,  who  stated  that 
they  were  extremely  unsatisfactory  for  study,  the  material 
having  been  allowed  to  dry  and  being  poorly  preserved,  and 
that  therefore  he  could  not  make  a  positive  diagnosis;  he 
added  that  round-celled  sarcoma  could  not  be  excluded.  Four 
weeks  after  the  operation,  a  recurrence  set  in  which  grew  rapidly, 
soon  reaching  the  size  of  a  fist,  and  extending  from  the  mastoid 
to  the  clavicle. 

The  case  was  considered  inoperable  by  Dr.  Fowler,  who  then 
started  the  toxin  treatment,  April  lo,  1913.  After  five  or  six 
injections  the  tumor  began  to  soften,  and  it  opened  sponta- 
neously, discharging  necrotic  material  and  gradually  decreasing 
in  size  so  that  in  the  early  part  of  May,  Dr.  Fowler  regarded  the 
trouble  as  practically  cured,  and  he  diminished  the  size  of  the 
dose  of  toxins.  When  he  had  gone  back  from  14.5  minims  to  8.5 
minims,  the  tumor  began  to  increase  again  very  rapidly,  where- 
upon the  doses  were  again  increased.  I  first  saw  the  patient 
on  the  15th  of  May,  and  on  physical  examination  found  an  old 
cicatrix  two  inches  long,  about  an  inch  below  the  angle  of  the 
jaw,  extending  over  to  the  chin.  There  were  two  recent  cica- 
trices at  the  site  of  the  old  healed  sinuses.  In  the  anterior 
portion  of  the  neck,  beginning  a  little  to  the  left  of  the  median 
line  and  extending  downward  to  the  angle  of  the  jaw,  was  a  mass 
about  two  and  a  half  inches  in  diameter  laterally,  very  firm  in 
consistence  and  much  harder  than  ordinary  sarcoma,  more  like 
carcinoma.  There  were  several  other  smaller  and  discrete  tumors 
in  the  cervical  and  supraclavicular  regions.  Skin  adherent  only 
in  the  region  of  the  cicatrix,  and  not  reddened.  Tumor  not 
attached  to  the  trachea  or  thyroid  cartilage.  General  condition 
good,  but  the  patient  had  lost  fifteen  pounds  in  weight.  I 
urged  pushing  the  toxins  to  the  limits  of  safety,  and  after  in- 
creased doses  his  condition  quickly  showed  signs  of  improve- 
ment. The  improvement,  continued,  and  when  seen  on  July 
17,  1913,  the  tumors  in  the  cervical  and  submental  regions  had 


coley:  neoplasms  of  the  lymphatic  glands  23 

almost  completely  disappeared,  and  his  general  condition  was 
good.  The  dose  of  the  toxins  had  been  carried  up  to  20  minims 
given  in  the  pectoral  region. 

Physical  examination  January  20,  1914,  shows  the  neck 
entirely  normal.  There  is  no  suspicion  of  any  enlarged  glands. 
The  patient's  weight  has  increased  from  212  to  222  pounds. 

The  patient  has  continued  in  good  health  up  to  the  present 
time,  December,  191 5. 


Fig.  23. — Case  VIII.     Angiopapillary  endothelioma  of  neck.      Specimen  from 
exploratory  operation. 

Case  VIII. — Round-celled  angiosarcoma  of  neck  or  adenocar- 
cinoma. 

Mr.  K.,  aged  forty- three  years,  was  referred  to  me  by  Dr. 
J.  A.  Bodine,  of  the  New  York  Polyclinic  Hospital,  on  March 
14,  191 1,  with  the  following  history: 

Fifteen  months  before,  he  first  noticed  a  tumor  in  the  left 
cervical  region  which  increased  in  size  and  finally  involved  a  num- 


24  coley:  neoplasms  of  the  lymphatic  glands 

ber  of  the  glands  in  the  cervical  and  supraclavicular  regions.  An 
attempt  to  remove  the  tumor  had  been  made  by  Dr.  Bodine  at 
the  Polyclinic  Hospital  two  weeks  previously,  but  the  growth 
was  found  too  extensive,  and  it  was  impossible  to  make  a  com- 
plete removal.  The.  patient  was  referred  to  me  for  treatment 
with  the  mixed  toxins.  At  the  time  of  his  admission  to  the 
General  Memorial  Hospital  he  showed  a  recent  cicatrix  three 
inches  long,  just  above  the  clavicle,  extending  up  to  the  cervical 


Fig.  24. — Same  case  as  Fig.  23.     Papillary  adenocarcinoma  of  neck  (thyroid  ?). 
Specimen  from  removal  of  most  of  tumor.     Third  operation. 

region,  only  partly  healed;  there  was  an  irregular  tumor,  about 
two  and  a  half  inches  in  diameter,  ulcerated  in  the  centre,  and 
several  outlying  tumors,  more  or  less  intimately  connected 
with  the  main  mass  extending  down  to  and  beneath  the  clavicle. 
The  tumor  had  every  appearance  of  sarcoma.  Dr.  Bodine  stated 
that  the  microscopic  examination  had  shown  the  growth  to 
be  a  round-celled  sarcoma.  Dr.  Jeffries,  stated  it  was  an 
adenosarcoma.    The  patient  was  put  upon  the  mixed  toxins,  the 


coley:  neoplasms  of  the  lymphatic  glands  25 

injections  being  made  chiefly  in  the  pectoral  region,  four  to  five 
times  a  week.  At  the  end  of  one  week  there  was  decided 
improvement,  the  sluggish  ulcerating  surface  had  become  nearly 
healed,  the  tumor  had  decreased  in  size  and  was  more  freely 
movable.  The  improvement  continued  steadily  until  in  June 
all  that  remained  was  a  small  fibrous-feeling  mass,  about  the 
size  of  a  hazel-nut,  just  above  the  clavicle,  anterior  to  the 
sternomastoid  muscle.  This  was  freely  movable  and  could  have 
been  easily  removed  by  operation.  The  patient  has  been  steadily 
gaining  in  weight  during  the  last  four  weeks.  The  highest  dose 
of  toxins  given  in  this  case  was  7  minims,  which  usually  was 
followed  by  a  good  reaction  Physical  examination,  July  15,  191 1, 
showed  only  a  small  movable  mass  about  three-fourths  inch  in 
diamete  r,  just  above  the  clavicle,  which  felt  more  like  fibrous 
tissue  than  a  tumor.     His  general  condition  was  excellent. 

The  patient  then  left  the  hospital  and  I  lost  sight  of  him 
until  June  21,  19 14,  when  he  returned  to  me  with  the  following 
history:  He  stated  that  he  had  remained  well  until  about 
two  months  before,  when  a  local  recurrence  was  noticed  above 
the  left  clavicle;  the  tumor  grew  very  rapidly  with  occasional 
hemorrhages  and  some  ulceration. 

Physical  examination  showed  a  large  tumor  in  the  left  cervi- 
cal and  supraclavicular  region,  the  size  of  a  hen's  egg,  made  up 
of  nodules  or  less  fused  together.  It  is  soft  in  consistence,  with 
an  ulcerating  area  in  the  centre  which  bleeds  freely.  General 
health  fair.  The  tumor  measured  two  and  a  half  inches  by  four 
inches  in  diameter.  There  is  some  dulness  over  the  midsternum, 
which  would  indicate  involvement  of  the  midsternal  glands  as 
well. 

The  toxins  were  again  started,  most  of  the  injections  being  made 
in  the  buttocks,  although  a  few  doses  were  given  into  the  tumor 
itself.  Growth  continued,  though  not  as  rapidly  as  before; 
the  tumor  seemed  fairly  movable  and  it  was  decided  to  remove 
as  much  as  possible  by  operation,  which  was  done  on 
At  this  time  the  tumor  was  the  size  of  half  an  orange,  and  occu- 
pied the  whole  left  supraclavicular  region  extending  from  the 


26  coley:  neoplasms  of  the  lymphatic  glands 

inner  end  of  the  clavicle  nearly  to  the  outer.  It  proved  to  be 
extremely  vascular  and  extended  down  behind  the  clavicle  and 
was  found  in  intimate  relationship  with  the  pneumogastric  nerve, 
common  carotid  artery  and  subclavian  vein.  It  was  dissected 
off  from  the  carotid  with  difficulty. 

On  separating  the  base  of  the  tumor  from  the  attachment 
below,  the  subclavian  vein  was  apparently  wounded  and  a 
hemorrhage  ensued  which  it  was  difficult  to  control. 

One  of  the  smaller  nodules  above  the  clavicle  was  removed 
for  microscopic  examination,  and  Dr.  Ewing  pronounced  it  a 
lymphangioma.  The  specimen  was  evidently  too  small  to  show 
the  true  nature  of  the  tumor. 

The  tumor  extended  beneath  the  clavicle  and  no  attempt  was 
made  to  remove  it  completely.  The  wound  healed  kindly  and 
no^  further  hemorrhage  occurred.  After  he  had  recovered 
sufficiently,  he  was  again  put  upon  the  mixed  toxins,  plus  :r-rays. 
Up  to  the  present  time  there  is  no  apparent  recurrence  of  the 
growth.  The  report  of  the  microscopic  examination  of  the 
large  tumor,  by  Dr.  Ewing,  was  adenocarcinoma.^     (Fig.  25.) 

Case  IX. — Round-celled  sarcoma  of  the  glands  of  the  neck. 
Successfully  treated  with  the  mixed  toxins  of  erysipelas  and 
Bacillus  prodigiosus;   well  two  years. 

H.  W.,  male,  aged  fifty-five  years.    Patient  had  been  in  good 

health  until  the  early  part  of  May,  1913,  when  he  noticed  a 

small  painless  lump  appear  just  under  the  jaw  on  the  right  side, 

in  the  region  of  the  submaxillary  glands.     The  nodule  grew 

rapidly  in  size  and  was  operated  upon  by  Dr.  Frederick  B. 

Sweet,  of  Springfield,  Mass.,  who  found  a  tumor  about  the  size  of 

a  pecan  nut,  which  shelled  out  of  its  capsule  like  a  pea  from  its 

pod.     There  was  no  infiltration  of  the  surrounding  tissues  nor 

was  the  tumor  attached  to  the  bone.    Microscopic  examination 

proved  the  growth  to  be  round-celled  sarcoma.     Shortly  after 

the    operation    another    gland    developed    beneath    the    right 

1  November  15,  19 15.  Examination' shows  no  local  recurrence  but  during 
the  past  three  weeks  he  has  developed  marked  hoarseness,  which  is  probably- 
due  to  mediastinal  involvement.  December  25,  growing  rapidly  worse.  Died 
January  i,  1916. 


coley:  neoplasms  of  the  lymphatic  glands 


27 


sternomastoid  muscle.  This  was  removed  by  operation,  and 
found  lying  between  the  carotid  and  interna]  jugular  vein,  about 
the  size  of  a  small  cherry.  A  portion  was  removed  and  sent 
to  Dr.  Ewing,  whose  report  reads: 

"June  12,  1 9 13.  "The  material  shows  a  process  which  I 
should  call  lymphosarcoma.  It  is  somewhat  peculiar  in  that 
the  cell  type  is  not  very  typical,  but  mitotic  figures  are  abundant 
and  the  structure  of  glands  is  obliterated.  I  assume  that  there 
is  no  leukemia." 


Fig.  25. — Case  IX.  Lymphosarcoma  of  neck;  recurrence  after  three  opera- 
tions; condition  then  inoperable.  Entire  disappearance  and  patient  well  for 
two  and  one-half  years. 

Within  a  week  of  this  operation  a  rather  diffused  swelling 
developed  at  the  site  of  the  incision.  No  attempt  at  removal 
was  made  for  fear  of  injuring  the  facial  nerve.  Patient  entered 
the  General  Memorial  Hospital,  June  5,  1913,  for  the  mixed 
toxin  treatment.  The  toxins  were  given  in  gradually  increasing 
doses  but  no  reactions  were  obtained  until  8  minims  had  been 


28  coley:  neoplasms  oe  the  lymphatic  glands 

reached.  There  was  no  temperature  from  the  smaller  doses, 
although  they  caused  considerable  depression.  During  the 
earlier  period  of  the  treatment  two  to  three  very  small  glands 
appeared  at  the  site  of  the  second  operation  over  the  carotid 
vessels.  These  grew  slowly  until  they  reached  the  size  of  a 
hazel-nut.  After  the  first  reaction  was  obtained  there  seemed  to 
be  no  further  increase  in  the  size  of  these  growths.  Patient  re- 
turned home  July  26,  and  the  toxins  were  continued  by  his  family 
physician,  Dr.  Shores,  three  times  a  week  in  doses  ranging  from 
7  to  9  minims.  On  my  return  from  Europe,  the  end  of  August, 
patient  came  to  me  for  examination  and  advice.  I  found  that 
the  glands  in  the  neck  had  not  increased  any  in  size  during  my 
absence  and  that  there  was  no  return  of  the  tumor  in  the  sub- 
maxillary region,  which  had  disappeared  under  the  toxins.  In 
order  to  lessen  the  severity  of  the  treatment,  and  also  in  the 
hope  of  increasing  the  chances  of  controlling  the  disease,  I  decided 
to  again  operate  and  remove  the  tumors  in  the  carotid  region, 
for  which  purpose,  patient  reentered  the  hospital  on  Septem- 
ber 4,  1913.  I  found  tumors  very  deeply  placed  about  the  caro- 
tid vessels,  and  removed  three  growths  ranging  from  the  size  of 
a  pecan  to  that  of  a  hazel-nut.  Microscopic  examination  showed 
them  to  be  round-celled  sarcoma.  There  were  undoubtedly  a 
few  smaller  growths  situated  higher  up,  which  were  not  removed 
the  wound  was  fulgurated  for  five  minutes.  The  toxins  were 
immediately  resumed  and  the  dose  pushed  to-  9  minims  which 
gave  a  good  reaction.  On  September  11,  the  patient  left  the 
hospital  and  returned  home  where  the  treatment  was  continued 
three  times  a  week  for  two  months,  after  which  he  received  one 
week's  respite.  He  came  to  see  me  on  December  2,  1913,  at  which 
time  I  found  his  weight  to  have  increased  considerably,  and  the 
condition  of  his  neck  revealed  no  trace  of  the  former  tumor. 

The  toxins  were  continued  for  upward  of  one  year;  total 
number  of  doses,  150;  highest  dose,  9  minims.  Last  examina- 
tion, November  i,  191 5,  shows  no  trace  of  recurrence;  patient's 
general  health  excellent;  weight  normal.  Well  two  and  a  half 
years. 


coley:  neoplasms  of  the  lymphatic  glands  29 

Case  X. — Small  round-celled  sarcoma  of  neck. 

A.  W.,  aged  forty-nine  years;  admitted  to  my  service  at  the 
New  York  Cancer  Hospital  in  1894;  family  history  good. 
The  patient  had  first  noticed  a  small  tumor  just  beneath  the 
arigle  of  the  jaw  on  the  right  side  of  the  neck  six  months  before; 
this  grew  very  rapidly  but  was  accompanied  by  little  or  no 
pain;  it  was  associated  with  repeated  attacks  of  quinsy.  At 
the  time  when  he  entered  the  hospital,  the  tumor  was  the  size 
of  an  orange,  fixed  to  the  deeper  structures;  the  skin  was  not 
adherent.  Under  cocaine  a  portion  of  the  tumor  was  removed 
for  microscopic  examination  which  showed  it  to  be  a  small  round 
celled  sarcoma.  The  patient  was  put  upon  the  mixed  toxins 
of  erysipelas  and  Bacillus  prodigiosus,  which  caused  very  severe 
reactions.  Very  remarkable  improvement  followed  the  treat- 
ment; within  one  week  the  tumor  was  reduced  from  the  size 
of  an  orange  to  a  hen's  egg  and  became  freely  movable;  there 
was  no  sign  of  breaking  down  of  the  tumor.  The  injections  were 
continued  and  pushed  to  the  limit  of  tolerance.  No  further 
decrease  in  size  followed  however,  and  very  shortly  the  tumor 
began  to  increase  again  and  grew  as  rapidly  as  before,  later 
involving  the  pharynx  and  tonsil.  Whether  or  not  the  tumor 
was  primary  in  the  tonsil  is  not  clear.  The  tumor  in  the  neck 
was  noticed  before  any  increase  in  the  size  of  the  tonsil  was  noted. 
The  patient  died  two  weeks  later.  The  entire  duration  of  the 
disease  in  this  case  was  only  about  eight  months. 

Case  XL — Small  spindle-celled  sarcoma  of  the  cervical  and 
supraclavicular  glands  and  mediastinal  glands  held  under  control 
for  nearly  three  years  with  the  toxins.    Final  result,  death. 

J.  M.,  male,  aged  twenty-seven  years,  was  referred  to  me  by  Dr. 
Edgerton  in  October,  191 1,  with  the  following  history:  Four 
years  ago  he  had  glands  removed  from  the  neck  at  the  Polyclinic 
Hospital,  which  were  thought  to  be  tubercular.  The  disease 
recurred  and  increased  steadily  in  size  and  six  months  ago  a 
second  operation  was  performed  by  Dr.  Edgerton  at  the  New 
York  Hospital.  Microscopic  examination  of  the  glands  removed 
from  the  neck  and  supraclavicular  region  showed  the  disease  to 
be  spindle-celled  sarcoma. 


30  coley:  neoplasms  of  the  lymphatic  glands 

When  the  patient  came  to  me  in  October,  191 1,  he  was  put 
upon  the  mixed  toxins  in  gradually  increasing  doses  up  to  8 
minims,  which  were  followed  by  rather  severe  reactions  and  con- 
siderable decrease  in  the  size  of  the  tumor.  He  left  the  hospital, 
and  when  I  saw  him  again  in  March,  191 2,  physical  examina- 
tion showed  him  in  good  general  health,  except  that  he  had  a 
severe  cough.  There  was  marked  fulness  just  above  the  supra 
sternal  and  supraclavicular  region,  especially  on  the  left  side. 
No  distinct  tumor  could  be  felt,  but  a  general  infiltration  of  the 
tissues  had  taken  place.  There  were  several  old  cicatrices  in 
the  left  supraclavicular  region.  He  was  also  examined  by  Dr.  W. 
L.  Culbert,  who  found  the  left  side  of  the  larynx  considerably 
encroached  upon  by  the  tumor.  The  toxines  were  given  at 
irregular  intervals,  as  the  patient  would  not  give  up  his  work, 
and  had  to  be  treated  as  well  as  was  possible  as  an  out-patient, 
which  made  it  impossible  to  give  him  doses  large  enough  to 
produce  good  reactions.  On  January  13,  19 13,  he  was  readmitted 
to  my  service  at  the  General  Memorial  Hospital,  where  he  was 
treated  with  subcutaneous  and  intravenous  injections  of  the 
toxins,  under  which  treatment  the  tumor  showed  some  retrogres- 
sion. He  received  in  all  sixteen  treatments,  the  highest  dose 
being  7  minims,  which  was  followed  by  a  chill  and  temperature 
of  100.°  He  again  left  the  hospital  on  February  8,  1913,  after 
which  the  treatment  was  continued  rather  irregularly. 

In  the  spring  of  19 14  he  was  taking  the  toxins  only  once  or 
twice  a  week  in  small  doses,  as  he  did  not  wish  the  treatment 
to  interfere  with  his  occupation.  During  the  summer  the  tumor 
showed  slight  increase  in  size  and  when  the  treatment  was 
discontinued  entirely  during  August  and  September,  the  increase 
became  very  pronounced.  He  was  urged  to  return  to  the  hos- 
pital for  more  systematic  treatment,  but  failed  to  do  so  until 
November  18,  when  the  tumor  had  reached  considerable  size 
and  he  had  developed  a  hacking  cough,  due  to  pressure  of  the 
growth  upon  his  trachea  and  mediastinum.  Under  two  to 
three  weeks'  treatment  the  tumor  above  the  clavicle,  which 
was  the  size  of  a  goose-egg,  became  softer  and  under  ether  an 


coley:  neoplasms  of  the  lymphatic  glands  31 

incision  was  made  and  a  large  amount  of  partially  necrotic 
tumor  tissue  removed.  The  disease  apparently  extended  beneath 
the  clavicle  and  mediastinum  and  no  radical  operation  was 
possible.  Microscopic  examination  of  the  tissue  was  made  by 
Dr.  Ewing,  whose  report  read:  small  spindle-celled  sarcoma. 
The  disease  progressed  with  extreme  rapidity,  involving  pleura 
and  lungs  and  causing  death  one  month  later. 

II. — malignant  tumors  of  tonsil  and  neck 

Case  XII. — Inoperable  spindle-celled  sarcoma  of  the  tonsil  and 
nasopharynx  {for  full  report  see  Medical  Record,  November  17, 
1894). 

Male,  aged  thirteen  years,  had  a  rapidly  growing  tumor, 
starting  apparently  in  the  tonsil  and  extending  up  into  the 
nasopharynx,  seriously  interfering  with  the  patient's  breathing. 
A  portion  of  the  tumor  was  removed  and  examined  by  a  compe- 
tent pathologist,  who  pronounced  it  spindle-celled  sarcoma.  I 
saw  the  patient  in  consultation  with  Dr.  Walter  B.  Johnson 
(Paterson,  N.  J.),  in  October,  1893,  at  which  time  the  clinical 
appearance  was  that  of  an  inoperable  malignant  tumor.  The 
toxin  treatment  was  started  by  me  and  later  carried  out  under 
my  direction,  by  Dr.  Johnson.  Under  three  months'  treatment 
(local  and  systemic  injections)  the  tumor  entirely  disappeared. 

He  was  examined  by  Dr.  Johnson,  June,  191 5,  and  found  to 
be  in  good  health  twenty- two  years  after  treatment. 

Case  XIII. — Inoperable  round-celled  sarcoma  of  the  tonsil  and 
neck  successfully  treated  with  the  mixed  toxins. 

A.  L.,  female,  aged  eleven  years.  Hartford,  Conn.  The  patient 
was  referred  to  me  by  Dr.  William  R.  Porter,  of  Hartford,  on 
November  8,  1906.  The  patient  had  always  been  in  good  health, 
except  that  she  had  frequent  attacks  of  tonsillitis.  A  year  ago  she 
had  a  small  swelling  in  one  of  the  glands  on  the  right  side  of  the 
neck.  The  mother  does  not  know  whether  it  entirely  subsided 
or  not.  Two  months  ago  she  noticed  considerable  enlargement 
in  this  region,  which  increased  rather  rapidly.    When  examined 


32  coley:  neoplasms  of  the  lymphatic  glands 

by  Dr.  Porter  in  the  latter  part  of  October  he  discovered  a  large 
tumor,  apparently  originating  in  the  right  tonsil  and  nearly 
blocking  up  the  pharynx.  She  was  examined  by  Dr.  McKnight 
and  a  number  of  other  physicians  in  Hartford,  and  all  considered 
the  tumor  inoperable.  The  patient  was  referred  to  me  by  Dr. 
Porter  on  November  8,  1906.  Physical  examination  at  this  time 
showed  a  growth  the  size  of  half  a  hen's  egg,  0I1  the  right  side  of 
the  neck,  involving  the  pharynx  wall  and  tonsil,  nearly  blocking 
up  the  passage.  On  the  opposite  side  of  the  neck,  just  below 
the  angle  of  the  jaw,  there  is  a  tumor  about  the  size  of  a  small 
hen's  egg,  fairly  movable,  smooth  in  outline,  fairly  firm  in  con- 
sistence, skin  not  adherent.  Diagnosis:  round-celled  sarcoma 
of  tonsil  and  neck.  The  toxins  were  begun  November  9,  1906, 
and  continued  with  two  or  three  intervals  to  rest,  one  of  three 
weeks  in  duration,  up  to  the  middle  of  May,  1907,  the  patient 
receiving  in  all  between  eighty  and  ninety  injections,  nearly 
all  of  which  were  given  in  the  pectoral  region ;  a  few  were  given 
into  the  tumor  of  the  neck,  but  none  into  the  tonsil.  After  two 
or  three  weeks'  treatment  there  was  a  marked  softening  of  both 
neck  and  tonsil  tumor.  Examination  in  consultation  with  Dr. 
W.  L.  Culbert;  the  latter  removed  a  portion  of  the  tumor  of 
the  tonsil,  and  it  was  found  that  the  central  portion  of  the  same 
had  become  entirely  necrotic,  and  several  drams  of  broken-down 
tumor  tissue  were  curetted  out.  I  also  removed  some  tissues 
from  the  tumor  of  the  neck,  which  also  proved  softened  and 
necrotic  in  the  centre.  Both  specimens  were  examined  at  the 
Loomis  Laboratory  by  Drs.  Tracy  and  Buxton,  and  both  proved 
to  be  round-celled  sarcoma. 

This  patient  was  rather  susceptible  to  the  toxins,  and  was 
rarely  able  to  stand  more  than  2  or  3  minims  without  a  severe 
chill  followed  by  a  temperature  of  103°  to  105°.  The  highest 
temperature  was  106°. 

In  two  months  the  tumor  of  the  tonsil  and  the  neck  had 
entirely  disappeared.  Shortly  afterward  a  new  swelling  devel- 
oped in  the  neck,  about  one  inch  higher  up.  This  swelling  per- 
sisted for  a  long  time  in  spite  of  continued  and  severe  treatment. 


coley:  neoplasms  of  the  lymphatic  glands  33 

She  also  developed  a  small  glandular  tumor  on  the  other  side 
of  the  neck  beneath  the  sternomastoid  muscle.  In  February, 
while  taking  the  treament,  she  had  a  severe  attack  of  herpes, 
involving  the  right  pectoral  region  and  entire  right  arm.  This 
was  extremely  painful,  and  she  was  unable  to  take  the  treatment 
for  about  three  weeks.  In  the  early  part  of  May  there  still 
remained  some  swelling  in  both  sides  of  the  neck,  rather  deeply 
seated,  underneath  the  sternomastoid  muscle,  and  I  decided 
to  explore  under  ether.  I  found  the  swelling  consisted  entirely 
of  broken-down  necrotic  material  which  had  not  found  an  easy 
exit.  Some  of  the  tissues  from  both  sides  were  sent  to  Dr. 
Tracy  of  the  Loomis  Laboratory,  and  microscopic  examina- 
tion showed  no  evidence  of  sarcoma  remaining.  The  wound 
quickly  healed.  The  patient  was  shown  before  the  Hartford 
Medical  Society  on  May  27,  1907,  apparently  perfectly  cured, 
and  again  before  the  Clinical  Congress  of  Surgeons  of  North 
America,  in  November,  191 2,  in  good  health.  My  last  report 
was  received  in  January,  1916.  She  is  still  well,  eight  and 
a  half  years  later. 

Case  XIV. — Small  round-celled  sarcoma  of  the  tonsil  and  neck. 
Entire  disappearance  in  seven  weeks  under  treatment  with  the 
mixed  toxins  of  erysipelas  and  Bacillus  prodigiosus;  recurrence 
in  other  tonsil  and  other  side  of  neck  seven  years  later.  Very  rapid 
growth;  death  in  four  months. 

H.  M.,  male,  aged  thirty- two  years.  The  patient  was  referred 
to  me  on  October  17,  1905,  by  Dr.  Arpad  G.  Gerster,  of  New 
York,  as  a  case  of  inoperable  sarcoma  for  toxin  treatment,  with 
a  history  of  having  noticed  a  swelling  on  the  left  side  of  the  neck, 
just  behind  the  sternomastoid  muscle,  in  about  the  middle  of 
August,  1905.  At  about  the  same  time  he  also  noticed  an  en- 
largement of  his  left  tonsil;  there  was  no  pain  at  first,  but  as 
both  tumors  increased  rapidly  in  size,  they  soon  became  painful . 
In  the  latter  part  of  August,  1905,  the  patient  was  operated  upon 
at  St.  Mark's  Hospital  by  Dr.  Carl  Beck,  who  made  an  attempt 
to  remove  the  tonsil  tumor,  as  well  as  that  of  the  neck;  he  found 
it  impossible,  however,  to  make  a  complete  excision.    X-ray  as 


34  coley:  neoplasms  of  the  lymphatic  glands 

well  as  radium  treatment  was  tried  with  little  or  no  effect.  On 
October  13,  while  under  the  care  of  Dr.  Goldwater,  at  the  New 
York  Polyclinic,  a  portion  of  the  tonsil  tumor  was  removed  and 
examined  by  Dr.  F.  M.  Jeffries,  director  of  the  pathological 
laboratory  of  the  New  York  Polyclinic,  and  also  by  the  patho- 
logist of  the  Practitioners'  Laboratory,  both  of  whom  reported 
the  tumor  to  be  a  small  round-celled  sarcoma  (see  pathological 
reports  below). 

I  first  saw  the  patient  October  17,  1905,  and  found  the 
left  side  of  the  neck  occupied  by  a  soft  globular  tumor,  about 
the    size  of    half   an    orange;   it   extended  from  the   angle   of 


Fig.  26. — Case  XIV.     Sarcoma  of  neck. 

the  jaw  in  front  to  the  mastoid  process  behind  and  downward 
nearly  to  the  clavicle.  Examination  of  the  left  tonsil  showed 
it  enlarged  to  two  or  three  times  its  normal  size.  The  patient's 
general  health  had  been  but  little  affected.  He  was  admitted 
to  the  General  Memorial  Hospital  in  October  17,  1906,  and 
immediately  put  upon  the  mixed  toxins  of  erysipelas  and  Bacillus 
prodigiosus  without  any  other  treatment.  Daily  injections  were 
given,  alternately  into  the  neck  tumor  direct,  and  into  the 
pectoral  region.  The  highest  dose  given  was  7  minims;  his 
temperature  ranged  between  99.5°  and  103°.  In  less  than  a 
week  there  was  decided  decrease  in  the  size  of  the  tumors  and 


coley:  neoplasms  of  the  lymphatic  glands  35 

increase  in  mobility.  The  diminution  continued  steadily  until, 
at  the  end  of  six  weeks,  both  the  cervical  and  tonsil  tumor  had 
apparently  entirely  disappeared.  The  patient  left  the  hospital 
at  the  end  of  seven  weeks.  The  toxins  were,  however,  continued 
twice  a  week  for  some  time,  as  a  prophylactic  against  recurrence. 
He  remained  in  good  health  up  to  the  fall  of  191 1,  and  had  been 
shown  before  various  medical  society  meetings.     At  this  time 


Fig.  27. — Case  XIV.     (Third  operation,  April,  1912.) 

there  was  a  recurrence  in  the  tonsil  and  neck,  which  was  removed 
by  Dr.  Erdman,  December,  191 1.  Unfortunately  the  specimen 
was  lost.  The  growth  returned  very  rapidly,  and  in  less  than 
three  weeks  had  becom^e  larger  than  at  the  time  of  the  last 
operation.  In  January  15,  191 2,  the  patient  entered  my  service 
at  the  General  Memorial  Hospital  where  a  very  extensive  opera- 
tion was  performed  by  Dr.  William  A.  Downes  and  myself.  A 
mass  about  the  size  of  an  orange  and  several  smaller  masses  above 


36  coley:  neoplasms  of  the  lymphatic  glands 

the  clavicle  were  removed  as  well  as  the  entire  sternomastoid 
muscle.  These  tumors  were  carefully  examined  by  Dr.  Ewing, 
who  pronounced  them  round-celled  sarcoma.  The  patient  made 
a  good  recovery,  but  refused  to  remain  at  the  hospital  for  the 
toxin  treatment,  as  I  had  advised.  The  latter  was,  therefore, 
carried  out  for  a  few  weeks  by  his  family  physician,  when  the 
patient  lost  hope,  and  declined  further  treatment.  The  tumor 
grew  with  marked  rapidity  causing  death  within  less  than  two 
months  after  the  last  operation. 

Pathological  Reports,  October  17,  1905: 

(i)  "The  neoplasm  submitted  has  the  character  of  round-celled 
sarcoma.  The  cells  are  a  mixture  of  small  and  large.  The 
tumor  appears  decidedly  malignant,  and  has  probably  extended 
beyond  local  limits.  Examination  shows  that  the  cells  have 
invaded  the  bloodvessels,  and  could  easily  have  been  swept 
into  the  current. 

"(Signed)  Peactitioners'  Laboratory." 

(2)  December  21,  1911: 

"Specimen  consists  of  a  mass  of  tissue  removed  from  the 
tonsil. 

"Microscopic  examination  shows  the  following  changes: 

"The  tissue  is  irregularly  covered  externally  by  stratified 
squamous  epithlium.  The  main  volume  of  the  tissue  is  made 
up  of  round  cells,  the  nuclei  of  which  show  mitotic  figures. 
These  cells  are  closely  packed  together  and  show  no  attempt  to 
reproduce  the  lymphoid  follicles  normally  encountered  in  the 
tonsil.  The  cellular  foci  are  definitely  surrounded  by  connective 
tissue. 

"The  diagnosis  in  this  case  rests  between  a  sarcoma  of  the 
tonsil  and  a  granuloma.  From  the  histological  appearance  it 
is  quite  impossible  to  decide. 

"Blood  from  this  patient  fails  to  give  a  Wasserman  reaction." 

"(Signed)       Douglas  Symmers, 
"Acting  Pathologist  to  New  York  Hospital." 


coley:  neoplasms  of  the  lymphatic  glands  37 

Dr.  James  Ewing's  report  on  the  tumor  removed  by  me  on 
January  15,  1912,  showed  it  to  be  undoubtedly  a  "round-celled 
sarcoma." 

(3)  Pathological  Report,  dated  April,  1912: 

"Sections  show  a  diffuse  growth  of  medium-sized  round 
cells.  Nuclei  are  moderately  hyperchromatic ;  mitoses  are 
occasionally  seen.  No  reticular  stroma  is  visible  but  the  tumor 
is  infiltrating  the  muscular  and  fat  tissues  after  the  manner  of 
a  malignant  growth.     Diagnosis:  Lymphosarcoma. 

"(Signed)        James  Ewing." 

Case  XV. — Small  round-celled  sarcoma  of  the  tonsil  with  exten- 
sive metastases  on  both  sides  of  neck.  Entire  disappearance  under 
toxin  treatment.    Recurrence  one  year  later. 

Mr.  C,  aged  forty- two  years.  Marked  loss  of  weight;  referred 
to  me  by  Dr.  T.  J.  Reardon,  of  Boston,  May  29,  1906.  Physical 
examination  at  this  time  showed  a  large  tumor  in  the  right  tonsil 
nearly  blocking  up  the  pharynx;  it  had  the  typical  clinical 
appearance  of  sarcoma ;  metastases  occupied  both  cervical  regions 
extending  down  nearly  to  the  clavicle;  general  condition  mark- 
edly deteriorated.  The  prognosis  seemed  so  hopeless,  that  no 
microscopic  examination  was  made.  The  toxins  were  given  into 
the  pectoral  region  and  pushed  to  extremely  high  doses,  as 
much  as  20  minims  of  the  uniiltered  preparation  being  given 
which  were  followed  by  severe  reactions,  the  temperature  rising 
to  104°  to  105°.  There  was  considerable  decrease  in  the  size 
of  the  tumors  while  he  was  in  the  hospital,  but  his  general  con- 
dition was  bad  and  he  continued  to  lose  weight  under  the  treat- 
ment, so  that  it  was  not  considered  wise  to  continue  and  after 
he  had  thirty-one  injections  he  was  sent  home  for  an  interval  of 
rest.  The  improvement  continued  steadily  after  he  left  the 
hospital  and  at  the  end  of  four  months  the  tumors  of  the  tonsil 
and  neck  had  entirely  disappeared.  The  patient  stated  that  he 
had  taken  some  patent  medicine  for  a  time  after  he  left  the 
hospital.  In  June,  1907,  a  little  over  a  year  later,  there  was  a 
recurrence  in  the  right  side  of  the  neck,  and  he  again  returned 


38  coley:  neoplasms  of  the  lymphatic  glands 

to  me.  At  this  time  there  was  a  smooth  globular  swelling  in  the 
submaxillary  region  about  the  size  of  a  small  hen's  egg,  mod- 
erately soft  in  consistence  and  not  very  firmly  attached.  It  had 
the  typical  clinical  appearance  of  a  sarcoma.  I  removed  the 
tumor,  and  microscopic  examination  by  Drs.  B.  H.  Buxton  and 
E.  K.  Dunham  showed  it  to  be  a  small  round-celled  sarcoma. 
The  patient's  general  health  was  good.  I  advised  resumption 
of  the  toxin  treatment,  but  the  patient  refused  and  returned 
home.  Other  tumors  quickly  developed  in  the  neck  and  grew 
with  great  rapidity,  causing  death  within  a  year. 

This  case,  I  believe,  is  of  extreme  importance,  inasmuch  as  it 
shows  that  a  tumor  of  high  malignancy,  the  diagnosis  of  which 
was  confirmed  by  the  fatal  issue,  entirely  disappeared  together 
with  the  metastases  under  three  months'  treatment  with  the  tox- 
ins. The  subsequent  recurrence  with  the  diagnosis  this  time 
confirmed  by  microscopic  examination  removes  all  doubt  of  the 
nature  of  the  primary  tumor. 

Case  XVI. — Lymphosarcoma  of  the  tonsil  with  extensive  metas- 
tases in  the  glands  of  the  neck;  complete  disappearance  under  the 
toxins;  later  recurrence  no  longer  controlled  by  the  toxins;  death; 
autopsy. 

Mr.W-,  male,  aged  thirty-five  years,  a  patient  of  Drs.  McMullen 
and  Stanton,  Schenectady,  N.  Y.,  noticed  a  swelling  of  left 
tonsil  late  in  November,  1909.  A  few  weeks  later  he  noticed 
an  enlargement  of  the  glands  of  the  neck  on  the  left  side.  The 
tumors  grew  with  great  rapidity,  and  in  February,  1910,  had 
become  so  extensive  that  the  patient  was  sent  to  Dr.  George 
W.  Crile  for  operation,  if  he  considered  it  feasible.  Dr.  Crile 
found  a  tumor  nearly  blocking  up  the  pharynx,  and  the  neck 
tumor  so  large  that  he  did  not  beHeve  it  possible  to  do  a  radical 
operation,  and  at  once  put  the  patient  upon  the  mixed  toxins 
(Coley),  prepared  by  Dr.  Tracy,  of  the  Huntington  Cancer 
Research  Fund.  The  patient  was  emaciated  and  in  very  bad 
general  condition  at  the  time  the  treatment  was  begun.  At  the 
end  of  two  weeks  there  was  a  marked  decrease  in  the  size  of  the 
tumors.    The  patient's  general  condition  has  become  worse.    At 


coley:  neoplasms  of  the  lymphatic  glands  39 

the  end  of  five  weeks  tbe  tumors  had  nearly  disappeared.  In 
September  the  tonsil  again  enlarged  to  about  twice  its  normal 
size.  Sections  examined  by  this  showed  the  same  histological 
picture  as  at  the  previous  examination.  Lymphosarcoma.  He 
entered  the  Ellis  Hospital  on  September  7,  remaining  until  Sep- 
tember 28,  during  which  time  he  received  fifteen  injections  of  the 
toxins,  with  a  complete  disappearance  of  the  growth.  In  Sep- 
tember, 1 910,  I  examined  him  and  there  was  no  evidence  of  any 
tumor.  During  October  he  received  eight  injections;  November, 
seven  injections;  December,  seven  injections;  January,  six  in- 
jections. About  January  18  the  growth  again  appeared,  involv- 
ing the  tonsil  and  extending  along  the  anterior  pillar  and  along 
the  palate  anteriorly.  The  tonsil  was  about  three  times  its 
normal  size,  no  glandular  involvement.  During  February  he 
received  nine  injections;  March,  seven  injections.  While  nearly 
all  of  the  injections  were  made  in  the  pectoral  region,  a  few  were 
made  into  the  neck  tumor  itself,  and  one  directly  into  the  tonsil, 
causing  a  very  decided  local  reaction,  swelling  of  pharynx  and 
cervical  glands.  A  large  slough  of  the  upper  part  of  the  growth 
took  place.  Dr.  McMullen  stated  the  patient  was  getting  the 
injections  just  as  rapidly  and  in  as  large  doses  as  his  general 
condition  permitted  and  that  he  "hoped  to  have  the  growth 
again  cleared  up  in  a  short  time."  The  ultimate  result  is  still  in 
doubt. 

In  February,  191 1,  the  patient  was  referred  to  me  for  personal 
treatment  by  Drs.  McMullen  and  Stanton;  he  remained  under 
my  care  for  four  weeks,  during  which  time  the  toxins,  both 
filtered  and  unfiltered,  were  given  intravenously,  and  caused 
severe  reactions.  Temporary  improvement  occurred,  but  later 
the  toxins  seemed  to  have  little  effect  upon  the  tumor  which 
gradually  increased  in  size.  The  patient's  general  condition 
slowly  deteriorated  and  he  'died  on  February  7,  191 2. 

I  am  indebted  to  Drs.  McMullen  and  Stanton  for  the  follow- 
ing very  complete  postmortem  examination  report,  made  by 
Dr.  Kellert: 

"The  right  side  of  the  neck  is  greatly  enlarged  by  two  tumor 


40  coley:  neoplasms  or  the  lymphatic  glands 

masses,  the  smaller  one  of  which  is  approximately  5  cm.  in 
diameter  and  is  intimately  associated  with  the  inferior  maxilla. 
The  larger  mass,  approximately  10  cm.  in  diameter  and  of  oval 
shape,  is  situated  beneath  and  behind  the  above  mass.  From 
the  smaller  mass  there  extends  two  minute  openings  through 
the  skin  and  from  which  there  exudes  a  small  amount  of  puri- 
form  material.  In  the  medium  line  beneath  the  larynx  is  an 
incision  4  cm.  in  length,  at  the  lower  end  of  which  is  a  round 
opening  i  cm.  in  diameter  which  extends  into  the  trachea. 
Over  the  sacral  region  are  two  small  areas  of  ulceration.  Edema 
of  extremities  is  absent.    Median  incision  made. 

"The  organs  of  the  neck  were  removed  en  masse  and  the 
tumor  masses  above  described  are  seen  to  consist  of  a  grayish- 
white,  soft  friable  tissue  involving  the  glands,  which  extend 
downward  toward  the  clavicle.  The  glands  are  matted  together 
and  form  one  continuous  mass.  On  cut  section  the  tumor 
presents  numerous  irregular,  yellowish  white  softened  areas. 
The  upper  mass  has  a  centre  which  is  of  a  dark  greenish  color 
and  communicates  with  the  gland.  The  tissues  surrounding  the 
larynx  are  slightly  edematous.  The  mucous  membrane  of  the 
trachea,  below  the  larynx,  presents  a  reddened  injected  appear- 
ance.   The  tongue  is  negative." 

Dr.  McMuUen  adds: 

"The  remarkable  fact  about  the  autopsy  was  that  not  a  single 
metastasis  was  discovered  anywhere  outside  of  the  chain  of 
cervical  glands  which  drained  the  tonsil.  In  spite  of  the  long 
continued  use  of  such  large  doses  of  the  toxins  there  were  no 
remarkable  changes  in  either  the  heart,  muscle,  or  kidneys." 

A  microscopic  examination  was  made  by  four  pathologists, 
including  Dr.  Crile. 

Dr.  Swing's  report,  dated  January  22,  1913,  reads  as  follows: 

"The  material  consists  of  a  section  of  small  portion  of  sub- 
cutaneous or  submucous  tumor  nodule.  The  structure  is  that 
of  lymphosarcoma.  The  proliferating  cell  is  large,  mononuclear 
with  vesicular  nucleus,  granular  acidophilic  cell  body.  These 
are  found  diffusely  scattered  throughout  the  section.     No  giant 


coley:  neoplasms  of  the  lymphatic  glands  41 

cells;  few  traces  of  lymphocytes,  some  focal  necrosis  and  some 
traces  of  reticular  tissue.  The  cells  are  loosely  packed  and  tlie 
general  appearance  recalls  that  of  an  infectious  granuloma  with 
excess  of  large  round  cells.  The  true  neoplastic  nature  of  the 
process,  as  of  most  lymphosarcomas,  appears  doubtful." 

This  together  with  the  autopsy  report  render  the  case  par- 
ticularly complete  and  full  of  interest. 

Case  XVII. — Round-celled  sarcoma  of  tonsil  with  metastases 
in  neck.  Entire  disappearance  under  toxin  treatment;  no  recur- 
rence five  years  later. 

C.  W.,  male,  aged  thirty-six  years.  Family  history:  Uncle  died 
of  cancer  of  leg.  Patient's  general  health  always  good.  Referred 
to  me  by  Dr.  Skeels,  of  St.  Albans,  Vermont,  on  May  26,  1910. 
He  had  smoked  a  great  deal,  but  stopped  smoking  six  weeks  ago. 
He  first  noticed  a  swelling  in  the  right  tonsil  two  months  ago; 
two  weeks  ago  noticed  an  enlargement  of  the  gland  in  the  right 
side  of  the  neck.  He  was  treated  by  a  throat  specialist  for  some 
time,  but  the  tumor  increased  steadily  and  rapidly.  It  had  been 
pronounced  an  inoperable  malignant  tumor  by  four  prominent 
surgeons  of  Montreal.  Physical  examination  by  me  on  May  26, 
1910,  showed  the  right  tonsil  enlarged  to  the  size  of  an  almond, 
ulcerated  on  its  posterior  surface.  The  tumor  was  very  hard  on 
palpation,  resembling  carcinoma  rather  than  sarcoma;  there 
was  a  hard,  movable  gland  the  size  of  an  English  walnut  in  the 
right  cervical  region,  anteriorly  to  the  sternomastoid  muscle. 
The  patient  was  admitted  to  the  General  Memorial  Hospital 
and  remained  in  the  hospital  for  about  six  weeks.  A  portion 
of  the  tonsil  was  removed  for  microscopic  examination,  and 
pronounced  round-celled  sarcoma,  by  Dr.  W.  C.  Clark,  Pathol- 
ogist to  the  Hospital.  The  injections  were  practically  all  made 
into  the  pectoral  region  and  doses  ranged  from  0.5  minim  to  5 
minims,  with  fairly  severe  reactions  from  the  larger  doses.  The 
tumor  in  the  neck  first  became  softer  and  more  movable;  at  the 
end  of  a  week  it  began  to  decrease  in  size  with  final  disappear- 
ance under  four  weeks'  of  further  treatment.  The  tumor  of  the 
tonsil  diminished  more  slowly  but  at  the  end  of  two  or  three 


42  coley:  neoplasms  of  the  lymphatic  glands 

months  this,  too,  entirely  disappeared.  A  letter  from  the 
patient's  physician,  dated  March  19,  191 1,  stated:  "He  is  at 
present  perfectly  well;  there  is  absolutely  no  sign  of  any  growth 
in  his  tonsil;  his  recovery  here  is  considered  as  almost  miracu- 
lous." 

Later  Notes:  A  letter  received  from  the  attending  physician, 
Dr.  E.  J.  Melville,  under  date  of  July  10,  1913,  states: 

"  There  is  no  return  of  the  tumor  in  Mr.  W.'s  case  and  no  parti- 
cular change  in  his  condition  from  what  I  reported  to  you  six 
months  ago.  The  tumor  has  not  returned.  In  fact  the  tonsil 
and  peritonsillar  tissue  is  normal.  His  only  ailment  is  a  pro- 
gressive dementia^  probably  caused  by  ischemia  of  the  brain. 

''This  case  is  a  complete  cure,  with  no  return  to  date." 

Under  date  of  January  14,  1914,  Dr.  Melville  writes: 

"There  has  been  no  return  of  the  sarcoma  of  the  tonsil,  which 
disappeared  under  the  toxin  treatment  four  years  ago. 

"  Mr.  W.  is  about  the  same  as  when  I  wrote  you  last,  suffering 
from  ischemia  of  certain  areas  of  the  brain,  which  causes  a  form 
of  brain  softening,  and  progressive  dementia,  of  a  mild  idiotic 
type.  This  condition  is  probably  due  to  arteriosclerosis,  from 
which  disease  he  has  suffered  for  ten  years. 

"His  appetite  and  general  physical  condition  have  not  mate- 
rially changed  in  the  past  two  years." 

Last  note,  August  2,  1915,  five  years  after  treatment  Dr. 
Melville  writes  Mr.  W.  has  had  no  return  of  his  sarcoma  of 
tonsil,  but  his  mind  is  still  degenerating. 

Case  XVIII. — Lymphosarcoma  of  tonsil  and  pharynx  with 
metastases  in  the  neck. 

Mr.  C,  aged  forty-three  years.  Family  history  good; 
Wassermann  negative.  About  a  year  ago  he  noticed  enlarge- 
ment of  the  right  tonsil,  which  increased  in  size  from  time  to 
tinie  for  about  six  months.  Removal  of  tonsils  by  Dr.  Leonard 
at  the  St.  Bartholomew  Clinic.  A  local  recurrence  took  place 
and  grew  rapidly  until  November,  19 14,  when  the  growth  filled 
nearly  the  entire  pharynx.  In  December,  1914,  a  section  of  the 
original  specimen  removed  was  examined  by  Dr.  Dickson,  the 


coley:  neoplasms  of  the  lymphatic  glands  43 

pathologist  of  the  Eye  and  Ear  Infirmary,  who  pronounced  it 
small  round-celled  sarcoma,  which  diagnosis  was  subsequently 
confirmed  by  Dr.  James  Ewing.  On  January  31,  191 5,  the 
patient  was  admitted  to  the  General  Memorial  Hospital.  Physical 
examination  at  this  time  showed  a  tumor  of  the  right  tonsil, 
extending  nearly  over  to  the  opposite  pillar  and  blocking  up 


Fig.  28. — Case  XVIII.  Inoperable  lymphosarcoma  of  tonsil  and  neck. 
Nearly  disappeared  after  two  months'  toxin  treatment,  but  then  increased 
slightly.  Removed  by  operation  and  toxin  treatment  again  given.  Recurred ; 
marked  improvement.  Under  radium  and  x-rays.  Temporary;  still  under 
treatment,  but  getting  worse. 


the  whole  pharynx  and  reaching  up  behind  the  soft  palate, 
pushing  the  latter  forward  into  the  buccal  cavity.  The  toxins 
were  started  at  once,  the  injections  being  made  in  the  pectoral 
region;  the  initial  dose  was  0.5  minim  which  was  increased  by 
0.5  minim  daily  until  5  minims  were  reached,  which  produced 
a  chill  and  moderate  reaction.  After  three  or  four  injections, 
marked  diminution  in  the  size  of  the  tumor  was  noticed  and 


44  coley:  neoplasms  of  the  lymphatic  glands 

there  was  less  distress  in  swallowing.  The  tumor  continued  to 
decrease  in  size  rapidly  and  two  and  a  half  weeks  after  the 
treatment  was  started,  it  was  only  about  one-third  its  original 
size.  He  received  from  three  to  five  injections  a  week,  practic- 
ally all  systemic  and  the  highest  dose  given  was  9  minims;  he 
usually  had  one  or  two  reactions  a  week.  During  Aprilthe 
tumor  showed  little  change  in  size,  but  was  considerably  paler 
than  before  and  much  harder  in  consistence;  it  felt  like  fibrous 
tissue. 


Fig.  29. — Case  XVIII.     Lymphosarcoma  of  tonsil  and  neck;   after  toxins. 
There  is  increase  in  fibrous  tissue. 

Dr.  Welch's  report  on  the  slides  sent  him  reads  as  follows: 
"  March,  15  191 5.  "The  sections  show  along  one  edge  lamin- 
ated, flat  epithelium  with  many  wandering  cells.  Beneath  the 
epithelium  is  a  thin  ayer  of  rather  dense  fibrous  tissue,  here  and 
there  penetrated  by  the  cells  of  the  underlying  neoplasm.  There 
appears  to  be  no  ulceration.  The  rest  of  the  sections  is  composed 
of  a  densely  packed  mass  of  cells  belonging  to  the  lymphocytic 


coley:  neoplasms  of  the  lymphatic  glands  45 

group.  Many  of  these  cells  are  ordinary  lymphocytes,  but  the 
prevailing  cells  are  larger  with  round  and  oval  nuclei  presenting 
a  nuclear  membrane  and  one  or  more  nucleolar  particles  of 
chromatin.  These  latter  cells  have  a  fair  amount  of  cytoplasm, 
but  cellular  outlines  are  indistinct.  These  larger  cells  I  regard 
as  of  lympho  cytic  nature,  rather  than  fibroblastic.  There  are 
no  evidences  of  follicles  or  other  architectural  features  of  the 
tonsil.  There  are  occasional  strands  or  septa  of  connective 
tissue,  but  in  general  there  is  very  little  basement  substance  or 
tissue  between  the  cells.  Bloodvessels  are  recognizable,  but  do 
not  appear  to  be  abundant.    Nuclear  figures  are  numerous. 

"Diagnosis:  lymphoblastoma.  The  tumor  may  also  be  called 
a  round-celled  sarcoma,  although  I  consider  its  origin  to  be 
from  lymphatic  tissue.  Remark:  The  tumor  is  histologically 
to  be  regarded  as  malignant." 

The  toxins  were  continued  four  or  five  times  a  week  until  the 
middle  of  May,  191 5.  There  seemed  to  be  no  further  decrease 
in  the  size  of  the  tumor.  Under  ether  an  incision  was  made 
through  the  soft,  palate,  and  a  mass  about  the  size  of  an  English 
walnut  was  enucleated  with  the  finger.  Microscopic  examina- 
tion made  by  Dr.  Ewing  showed  it  to  be  lymphosarcoma. 

A  small  gland,  about  the  size  of  an  olive  was  removed  at  the 
same  time,  and  proved  to  be  lymphosarcoma  (see  illustration  of 
slides).  The  toxins  were  resumed  after  operation  and  continued 
until  the  middle  of  July.  Examination  at  this  time  showed  the 
general  condition  to  be  about  the  same.  There  was  some  thick- 
ening at  the  site  of  the  incision,  which  was  apparently  only 
scar  tissue.  There  has  been  no  increase  during  the  last  month 
The  patient  left  the  hospital  for  a  two  weeks'  vacation. 

On  his  return  the  small  indurated  area  at  the  site  where  the 
tumor  had  been  removed,  had  increased  markedly  in  size,  so 
that  at  this  time  there  was  a  tumor  about  one  inch  in  diameter, 
firm  in  consistence.  The  patient  was  again  put  upon  the  mixed 
toxins  and  at  the  end  of  two  weeks  the  growth  was  apparently 
checked  but  had  not  noticeably  decreased  in  size. 

He  then  had  an  application  of  80  mg.  of  radium  for  eight  hours. 


46  coley:  neoplasms  of  the  lymphatic  glands 

Under  the  combined  treatment  the  tumor  rapidly  diminished  in 
size,  and  soon  there  was  scarcely  more  than  an  indurated  edge 
at  the  site  of  the  growth. 

Later  Notes  (October  12,  191 5).  The  improvement  which 
followed  the  use  of  radium  proved  very  temporary,  and  in  spite 
of  x-ray,  radium,  and  toxin  treatment,  the  primary  tumor  not 
only  began  to  increase  in  size,  but  more  and  more  of  the  cervical 
glands  became  involved;  these  were  at  first  held  in  check  by  the 
ir-rays,  but  the  disease  gradually  progressed,  and  at  present 
there  is  little  hope  of  further  control. 

November  18,  191 5.  Patient  returned  to  the  General  Mem- 
orial Hospital  this  morning,  and  was  shown  at  the  cKnical 
conference.  Four  and  one-half  weeks  previous  he  developed  a 
severe  attack  of  pneumonia;  his  temperature  ranged  to  104° 
and  fell  as  low  as  95°  at  the  crisis.  During  this  period,  the 
glands  on  both  sides  of  the  neck  which  were  remarkably  enlarged 
entirely  disappeared.  Examinations  this  morning  shows  no  evi- 
dence of  a  tumor  in  the  tonsil  or  pharynx;  no  enlarged  glands 
are  palpable  in  the  cervical  region.  It  should  be  stated  that  he 
had  radium  treatment  in  the  pharynx  a  few  days  before  he 
developed  pneumonia.  Inasmuch  as  the  enlarged  glands  devel- 
oped while  he  was  receiving  the  radium  treatment,  and  the 
disease  had  been  only  temporarily  held  in  check  by  the 
a;-rays,  it  would  seem  a  reasonable  inference  thatthe  pneumonia 
infection  was  responsible  in  part  at  least  for  the  disappearance  of 
the  glands.  A  week  later,  November  25,  1915,  small  recur- 
rence in  tonsil  again  visible.  January  i,  1916,  disease  slowly 
progressing. 

III. — SARCOMA  or  axillary  glands 

Case  XIX. — Lymphosarcoma  of  axilla. 

Mrs.  J.  G.,  aged  forty-five  years.  Family  history  good.  In 
December,  1905,  first  noticed  a  lump  in  the  left  arm,  which 
slowly  increased  in  size  until  March,  1906,  when  it  was  removed 
by    operation.      The    operation   was    regarded    as   incomplete. 


coley:  neoplasms  of  the  lymphatic  glands  47 

Microscopic  examination  was  made  by  the  pathologist  of  the 
West  Pennsylvania  Hospital,  whose  report  reads: 

"The  tumor  is  composed  of  small  round  cells  of  about  the  size 
and  appearance  of  mononuclear  leucocytes  (sarcoma  cells)  with 
a  moderate  amount  of  intercellular  substance  and  shows  the 
reticulum  and  stroma  formed  by  branching  stellate  forms,  which 
is  characteristic  of  lymphosarcoma." 

The  patient  was  referred  to  me  March  25,  1906,  by  Dr.  K. 
I.  Sanes,  of  Pittsburgh,  Pa.,  who  stated  that  the  glandular  tumor 
was  adherent  to  the  axillary  vein;  but  it  was  impossible  to 
state  from  examination  whether  or  not  the  axillary  vein  itself 
was  involved;  I  advised  the  use  of  the  mixed  toxins,  which  were 
started  immediately  and  continued  for  a  number  of  weeks  by  the 
family  physician.  Two  years  later  (March  23,  1908)  I  received 
a  letter  from  the  patient's  husband,  which  stated:  "Mrs.  G. 
is  quite  well.  Has  been  troubled  recently  with  some  rheumatism 
and  during  summer  had  severe  attack  of  bronchitis  followed  by 
intercostal  neuralgia  brought  on  by  the  coughing.  On  conval- 
escing partly,  she  went  to  Cape  May  for  six  weeks,  and  a  specialist 
there,  who  treated  her  with  electricity,  stated  that  her  condi- 
tion had  nothing  to  do  with  her  old  trouble." 

In  a  letter  received  from  the  patient's  husband,  dated  Jan- 
uary 20,  1914,  he  states:  "Mrs.  G.  has  never  had  a  return  of  the 
trouble  for  which  the  toxin  treatment  was  administered,  and  is 
now  well  after  eight  years." 

Case  XX. — Lymphosarcoma  of  the  axillary  region. 

Mr.  C.  R.,  male,  aged  twenty-nine  years.  In  the  spring  of  1910, 
the  patient  was  operated  upon  by  Dr.  Samuel  Robinson,  of  Bos- 
ton, for  a  tumor  situated  in  the  right  axillary  region.  Microscopic 
examination  showed  the  growth  to  be  round-celled  sarcoma. 
A  second  operation  was  performed  by  Dr.  Robinson,  on  August 
8,  191 1,  for  what  was  supposed  to  be  a  recurrent  or  metastatic 
tumor  involving  the  right  axillary  glands.  The  portion  removed 
was  examined  by  Dr.  Homer  Wright,  pathologist  of  the  Massa- 
chusetts General  Hospital,  and  pronounced  lymphosarcoma. 
Two  weeks  later  the  patient  was  referred  to  me  for  toxin  treat- 


48  coley:  neoplasms  of  the  lymphatic  glands 

ment.  The  injections  were  started  by  my  associate,  Dr.  J.  P. 
Hoguet,  and  later  continued  by  the  family  physician  until 
January,  191 2,  at  which  time  there  was  no  trace  of  the  tumor 
left.  I  made  a  careful  examination  of  the  patient  in  October, 
1913,  over  two  years  after  treatment  was  begun,  and  found  him 
in  good  health,  with  no  sign  of  a  recurrence.  The  patient  remains 
well  at  present,  four  years  later. 

Case  XXI. — Sarcoma  of  the  axillary  and  cervical  glands  {Pos- 
sible Hodgkin's). 

E.  F.,  male,  aged  thirty-five  years.  Family  history  negative. 
In  August,  191 1,  first  noticed  a  swelHng  in  the  right  axillary 
region  which  continued  to  grow  until  at  the  end  of  eight  months 
it  had  reached  the  size  of  a  fetal  head.  First  operation  was 
performed  by  Dr.  V.  Gaudiani,  of  New  York,  in  April,  191 2,  at 
which  time  there  were  no  traces  of  inflammatory  trouble,  the 
skin  was  movable  and  not  adherent,  and  the  tumor  was  not 
attached  to  the  chest-wall.  There  were  a  few  glands  in  the 
supraclavicular  region;  spleen  not  enlarged;  no  dulness  in  the 
mediastinum.  Patient's  general  condition  good.  A  few  supra- 
clavicular nodules  were  left  behind  at  the  time  the  axillary 
tumor  was  removed.  Anatomical  examination  showed  glands 
of  various  sizes,  easily  detached  one  from  the  other,  almost  uni- 
form in  arrangement,  and  markedly  soft  in  consistence. 

Microscopic  examination:  Lymph  cells  seem  to  be  a  little 
enlarged  in  size  with  a  prevalent  type  of  eosinophiles  cells, 
occasionally  giant  cells  (not  typical  Langhans's  cells);  connec- 
tive-tissue hyperplastic  with  spaces  of  hyaline  degeneration. 
The  diagnosis  of  Hodgkin's  disease  was  made  by  Dr.  Ewing. 
It  was  regarded  as  sarcoma  by  Dr.  Elser,  and  a  third  patholo- 
gist inclined  to  believe  it  tuberculous. 

After  a  few  months  (July,  191 2)  Dr.  Gaudiani  removed  the 
other  few  nodules,  which  meanwhile  had  become  enlarged  and 
painful.  He  found  the  anatomical  condition  a  little  changed,  as 
a  few  glands  were  included  in  a  periglandular  inflammation 
and  one  of  the  nodules  had  a  necrotic  focus  as  large  as  a  bean. 
Shortly  after  a  few  nodules  appeared  again  in  the  neck  and  pec- 
toral region,  which  rapidly  diminished  under  x-ray  treatment. 


coley:  neoplasms  of  the  lymphatic  glands  49 

I  first  saw  the  patient  in  July,  19 13,  at  which  time  there  was 
a  mass  about  the  size  of  a  fist  beneath  the  pectoral  muscle; 
supraclavicular  and  cervical  glands  markedly  enlarged.  The 
toxins  were  then  started  by  me  at  the  Italian  Hospital,  and 
carried  out  by  Dr.  Guadiani  under  my  direction.  After  a  few 
weeks'  treatment,  on  account  of  the  marked  local  reactions 
which  followed,  the  patient  refused  further  treatment.  He  took 
a  trip  to  Italy  where  he  remained  four  months.  On  his  return 
to  New  York  he  was  examined  by  Dr.  Gaudiani,  who  stated 
that  he  found  the  mass  in  the  subclavicular  and  pectoral  region 
as  well  as  the  gland  in  the  supraclavicular  region,  to  have  entirely 
disappeared.  This  was  on  the  side  of  the  first  operation.  At 
the  time  of  the  last  operation,  Dr.  Gaudiani  states  that  he  left 
a  large  mass  behind.  In  the  right  carotid  and  left  axillary 
regions,  where  no  operation  had  been  performed  the  glands 
showed  some  slight  increase  in  size.  He  was  then  put  upon 
aresenic  treatment,  which  is  still  being  used  at  the  present  time. 
On  March  31,  191 5,  Dr.  Gaudiani  writes  that  the  patient's 
general  health  remains  good.  The  tumors  in  the  right  axillary, 
sub-  and  supraclavicular  regions  where  the  disease  started, 
disappeared  under  the  toxin  treatment,  and  there  has  been  no 
sign  of  a  recurrence  since.  The  left  axilla  is  now  occupied  by  a 
tumor  the  size  of  a  fist,  connected  with  the  lymph  glands.  Other 
lymph  glands  the  size  of  an  apple,  occupy  the  right  carotid 
region.  Patient  had  several  treatments  with  salvarsan,  although 
he  had  a  negative  Wassermann  reaction.  The  glands  have  all 
disappeared  and  he  is  now  well,  January  7,  1916. 

Case  XXII. — Round-celled  sarcoma  of  axilla. 

P.  W.,  female,  aged  twenty-seven  years,  cut  her  hand  on  a 
flower  vase  in  1893,  and  wore  a  bandage  for  two  weeks.  During 
this  time  a  small  lump  appeared  in  the  axilla  of  the  same  side. 
This  lump  never  disappeared  and  slowly  increased  in  size.  Two 
other  lumps  appeared  later  and  finally  the  three  lumps  became 
fused  into  one.  In  May,  1895,  the  tumor  had  reached  the  size 
of  a  hen's  egg.  It  continued  to  increase  in  size  and  in  January, 
1896,  Dr.  A.  J.  McCosh,  of  the  Presbyterian  Hospital  found 


50  coley:  neoplasms  of  the  lymphatic  glands 

it  impossible  to  remove  the  entire  growth.  The  portion  remain- 
ing increased  rapidly  in  size  and  gradually  the  entire  arm  became 
swollen.  The  patient  was  referred  to  me  in  August,  1896. 
Physical  examination  at  this  time  showed  a  tumor  the  size  of  a 
fist,  occupying  the  right  axillary  region  and  extending  backward, 
apparently  involving  the  clavicle  and  a  portion  of  the  scapula. 
Anteriorly  it  reached  to  the  border  of  the  sternum;  it  was 
firmly  adherent  to  the  chest  wall.  The  skin  was  a  bluish-purple 
in  color,  and  there  was  an  area  of  ulceration  three-fourths  inch  in 
diameter.  Her  general  condition  was  fair.  A  few  injections  of  the 
mixed  toxins  were  given,  but  it  was  not  considered  wise  to 
continue  them.     The  case  went  on  to  a  rapidly  fatal  termination. 

Case  XXIII. — Lymphosarcoma  or  endothelioma  of  axilla  recur- 
rent in  groin. 

P.  J.  B.,  male,  aged  sixty-seven  years,  referred  to  me  in 
January,  191 1,  by  Dr.  Ferbert,  of  Los  Angeles.  Family  history 
good;  no  tubercular  history.  Three  years  before  had  first 
noticed  a  small  enlarged  gland  in  the  left  axilla;  this  slowly 
increased  in  size.  Four  to  five  weeks  before  his  admission  to 
the  hospital  it  began  to  grow  very  rapidly,  doubling  in  size  within 
a  month.  Physical  examination  on  January  31,  191 1,  showed 
a  tumor  in  the  left  axilla  two  and  a  half  by  three  incjies  in  diam- 
eter, made  up  of  a  number  of  more  or  less  discrete,  enlarged 
glands  varying  in  size  from  a  hazel-nut  to  a  walnut,  partially 
fused  together,  making  one  tumor  mass.  Operation  was  done  on 
February  i,  under  ether  anesthesia.  The  tumor  mass  extended 
up  to  and  beneath  the  clavicle,  and  removal  was  regarded  as 
incomplete.  Immediately  after  the  operation  the  patient  was 
put  upon  regular  treatment  with  the  mixed  toxins  of  erysipelas 
and  Bacillus  prodigiosus  which  was  kept  up  for  three  weeks  at 
the  hospital  and  later  continued  by  Dr.  Ferbert  at  Los  Angeles. 
Microscopic  examination  of  the  tumor  was  made  by  Dr.  James 
Ewing,  whose  report  stated:  "The  tumor  is  a  sarcoma  of  the 
lymph  nodes."  In  a  later  report  Dr.  Ewing  pronounced  it 
■endothelioma.  Dr.  W.  C.  Clarke,  the  pathologist  at  the 
General  Memorial  Hospital  reported :  "round-celled  sarcoma." 


coley:  neoplasms  of  the  lymphatic  glands  51 

In  a  letter  dated  November  11,  191 2,  Dr.  Ferbert  stated  that 
the  patient  was  still  well.  In  September,  1913,  he  returned  to 
to  Dr.  Ferbert  with  a  recurrence  underneath  the  pectoralis  minor 
muscle,  attached  to  the  subclavian  vein.  This  was  removed 
and  the  toxins  were  resumed  as  a  prophylactic.  Most  of  the 
tumor  was  sent  to  me,  and  examination  made  by  Dr.  Ewing 
on  January  29,  1914,  proved  it  to  be  a  true  lymphosarcoma. 
The  report  adds:  "It  is  composed  of  rather  large  cells  quite 
different  from  the  spurious  lymphosarcomas  which  resemble 
Hodgkin's  disease." 

In  his  last  report,  dated  April  17,  191 5,  Dr.  Ferbert  states: 
"On  examination  today  I  found  no  recurrence  whatever." 

Case  XXIV. — Fibrosarcoma  or  neurosarcoma  primary  in  the 
right  axilla. 

Mrs.  W.  D.,  aged  thirty-three  years,  was  referred  to  me  by 
Dr.  Fredericks.  Downs,  of  Bridgeport,  Conn.,  in  September,  19 13, 
with  the  following  history.  Family  history  good.  Ten  years 
ago  she  noticed  a  small  lump  in  the  posterior  portion  of  the  right 
axilla,  following  slijortly  after  a  blow  received  by  striking  the 
axilla  against  a  door.  The  tumor  was  removed  by  Dr.  Hy. 
Blodget,  of  Bridgeport,  Conn.  There  was  apparently  no  micro- 
scopic examination  made  at  this  time.  Two  years  later  there 
was  a  local  recurrence  just  behind  the  original  tumor  involving 
the  lower  portion  of  the  scapula.  The  patient  consulted  Dr. 
Downs  who  removed  a  portion  of  the  scapula  together  with  the 
tumor.  Microscopic  examination  proved  the  disease  sarcoma. 
She  remained  well  for  nearly  two  and  a  half  years,  when  a  second 
recurrence  took  place  in  the  pectoral  region  on  the  same  side 
just  below  the  clavicle.  A  third  operation  was  done  by  Dr. 
Downs  who  removed  a  portion  of  the  fifth  and  sixth  rib  together 
with  the  tumor.  There  also  was  a  hard,  shghtly  protuberant 
tumor  mass  above  the  clavicle  which  was  not  operated  upon. 
A  small  sinus  persisted  after  the  operation.  The  patient  then 
received  a  month's  treatment  with  the  mixed  toxins,  and  a  little 
later  a  second  course  of  two  months'  duration,  during  which 
time  the  tumor  above  the  clavicle  entirely  disappeared.     In 


52  coley:  neoplasms  oe  the  lymphatic  glands 

November,  1910,  she  had  an  attack  of  pneumonia.  Shortly 
afterward  a  tumor  developed  at  the  inner  portion  of  the  cica- 
trix in  the  pectoral  region  and  grew  rather  rapidly  until  it  had 
reached  the  size  of  a  grapefruit,  being  quite  five  inches  pro- 
tuberant. The  patient  states  that  this  for  a  time  diminished 
apparently  spontaneously  to  about  half  its  former  size,  accom- 
panied by  marked  falling-off  in  general  health. 

Physical  examination  at  the  time  of  admission  to  the  General 
Memorial  Hospital  on  September  22,  19 13,  showed  in  the  middle 
of  the  right  pectoral  region,  between  the  nipple  and  clavicle, 
a  tumor  markedly  protuberant,  the  size  of  an  orange,  partly 
pedunculated  with  an  attachment  to  the  chest  wall  of  not 
more  than  one-half  the  diameter  of  the  tumor  itself.  The 
tumor  was  not  covered  by  skin,  reddish  in  color,  of  fungoid 
appearance,  but  there  was  very  little  exudate;  it  was  appar- 
ently not  highly  vascular.  There  was  also  a  hard  tumor  above 
the  clavicle  very  firmly  fixed.  An  ic-ray  of  the  chest  showed  a 
large  intrathoracic  mass,  apparently  as  large  or  larger  than 
the  extrathoracic  tumor.  In  addition  there  was  a  tumor  the 
size  of  a  goose  egg  in  the  axillary  region.  Under  ether  anesthesia 
I  removed  the  mass  in  the  pectoral  region  flush  with  the  chest 
wall,  but  no  attempt  was  made  to  follow  it  into  the  thoracic 
cavity.  There  was  some  hemorrhage  which  was  controlled  by 
gauze  dressing.  The  patient  made  a  good  recovery  and  was 
then  put  upon  the  mixed  toxins  of  erysipelas  and  Bacillus  pro- 
digiosus  which  were  given  up  to  the  time  she  left  the  hospital 
in  October,  191 3,  and  later  continued  at  home  by  her  local 
physician.  When  she  returned  to  the  hospital  in  May,  1914, 
she  had  gained  twelve  pounds  in  weight  and  there  was  no  sign 
of  a  local  recurrence.  The  axillary  tumor  which  showed  a 
tendency  to  infiltrate  the  surrounding  tissues  had  become  more 
movable  and,  under  ether,  I  removed  a  mass  the  size  of  a  hen's 
egg  from  the  axillary  region.  The  patient  was  again  put  upon 
the  mixed  toxins  and  returned  to  her  home  on  June  18,  1914. 
Microscopic  examination  of  the  second  tumor  was  made  by  Dr. 
Ewing,  whose  diagnosis  was  neurosarcoma. 


coley:  neoplasms  of  the  lymphatic  glands  53 

Physical  examination  of  the  patient  on  August  i,  191 5,  shows 
no  return  of  the  tumor  of  the  chest  wall,  but  a  slight  falling 
off  in  weight.  The  tumor  above  the  clavicle  is  slightly  larger. 
The  toxins  were  resumed. 


IV. — SARCOMA  OF  INGUINAL  GLANDS 

Case  XXV. — Sarcoma  of  groin  {clinical  diagnosis). 

H.  P.,  male,  age  seven  years,  was  referred  to  me  by  Dr.  E.  P. 
Swasey,  of  New  Britain,  Conn.,  on  November  8,  1910.  No  his- 
tory of  tuberculosis  or  malignancy  in  the  family.  The  patient 
received  a  kick  in  the  right  groin  by  another  boy  three  months 
ago.  A  few  days  later  a  swelling  appeared,  which  gradually 
increased  in  size  until  one  month  later  it  had  reached  the  size  of  an 
egg.  This  was  removed  by  Dr.  Swasey.  The  specimen  was  not 
examined  microscopically.  The  wound  did  not  heal  promptly 
and  a  gradual  thickening  of  the  surrounding  tissues  with  involve- 
ment of  the  pelvic  glands  followed. 

Physical  examination  on  November  8,  19 10,  showed  the 
patient  apparently  in  good  general  health.  Examination  showed 
considerable  swelling  of  the  whole  upper  portion  of  the  right 
thigh  and  inguinal  region.  Just  above  Poupart's  ligament 
there  were  two  incisions,  one  two  inches  the  other  two  and  a 
half  inches  long,  showing  no  tendency  to  heal,  filled  with  slug- 
gish, grayish  granulations.  Palpation  above  Poupart's  liga- 
ment showed  a  hard  mass,  the  size  of  an  English  walnut.  The 
toxins  were  advised  and  the  patient  was  admitted  to  my  service 
at  the  Hospital  for  Ruptured  and  Crippled.  The  toxins  were 
given  for  about  one  month  by  which  time  the  tumor  mass  had 
become  much  smaller  and  softer  and  under  ether  curettement  was 
carried  out.  The  swelling  of  the  leg  gradually  disappeared, 
and  the  wound  promptly  healed. 

On  January  17,  1914,  Dr.  Swasey  writes:  "I  saw  the  patient 
and  take  pleasure  in  reporting  that  he  is  in  excellent  health, 
over  three  years  afterward." 


54  coley:  neoplasms  oe  the  lymphatic  glakds 

Case  XXVI. — Sarcoma  of  the  inguinal  glands. 

E.  C.  B.,  male,  aged  twenty-one  years,  always  well  until 
January,  1908,  when  he  was  struck  in  the  left  groin  by  a  lever. 
One  week  later  he  noticed  a  swelling  at  the  point  of  injury. 
This  increased  steadily  in  size  and  in  February  2,  three  weeks 
after  the  injury,  was  removed  by  Dr.  Dudley  Carlton,  of 
Springfield,  Mass.  The  microscopic  examination  was  made  by 
Dr.  J.  F.  Butler,  of  Springfield,  Mass.,  who  pronounced  it  small, 
round-celled  sarcoma.  A  recurrence  took  place  shortly  after- 
ward in  the  inguinal  and  iliac  glands  and  the  patient  was  referred 
to  me  for  the  toxin  treatment.  Physical  examination,  March 
26,  1908,  showed  his  general  condition  good.  Examination  of 
the  left  groin  revealed  enlargement  of  the  inguinal  and  super- 
ficial ihac  glands;  skin  was  not  adherent  and  there  was  no 
tenderness;  the  tumor  was  of  moderately  firm  consistence. 
The  patient  entered  my  service  at  the  General  Memorial 
Hospital,  where  the  toxin  treatment  was  at  once  begun.  The 
injections  were  made  in  the  buttocks  and  continued  for  two 
weeks  in  doses  ranging  from  0.5  to  5  minims  followed  by  well- 
marked  reactions  a  temperature  up  to  104°.  At  the  end  of 
this  time  the  tumors  had  almost  completely  disappeared  and 
he  was  allowed  to  go  home  with  the  advice  to  have  the  toxins 
continued  by  his  family  physician.  The  treatment  was  carried 
out  rather  irregularly  during  the  summer  and  in  October  of 
the  same  year,  he  returned  to  my  service  with  evidence  of  a 
recurrence.  The  toxins  were  again  administered  for  a  period 
of  three  and  a  half  weeks,  partly  into  the  tumor,  and  partly  into 
the  buttocks,  with  good  reactions.  He  received  nineteen  injec- 
tions during  this  time.  He  was  then  sent  home  and  urged  to 
have  the  treatment  continued  for  another  three  or  four  months. 
When  last  heard  from  (January,  19 14),  six  years  after  operation, 
he  was  in  good  health  and  free  from  recurrence. 

Case  XXVII. — Lymphosarcoma  primary  in  the  inguinal  region. 

Mrs.   L.    S.,   aged   forty-seven   years.    Family  history:    one 

brother    died    of   tuberculosis.      On  admission  to  the   General 

Memorial  Hospital,  March,  1915,  physical  examination  showed 


coley:  neoplasms  of  the  lymphatic  glands  55 

a  multiple  glandular  enlargement.  Microscopic  diagnosis :  lym- 
phosarcoma. 

Previous  personal  history  negative ;  patient  had  had  diphtheria 
and  measles  when  a  child. 

Patient  had  always  been  in  good  healthy  until  two  years  ago, 
when  she  first  noticed  a  movable  glandular  swelhng  in  both 
inguinal  regions,  which  appeared  apparently  simultaneously. 
Shortly  after  she  noticed  several  small  nodules  in  the  anterior 
aspect  of  both  thighs,  also  of  simultaneous  appearance.  One  year 
later  a  nodule  was  excised  and  examined  microscopically,  pro- 
nounced sarcoma.  She  was  then  operated  upon  at  the  Fordham 
Hospital  by  Dr.  Kenyon,  one  week  later,  at  which  time  several 
glands  the  size  of  a  fist  were  removed  from  the  left  cervical  region. 
A  few  days  later  Dr.  Kenyon  again  operated,  removing  several 
nodules  from  the  right  thigh.  The  patient  returned  home,  and 
shortly  after  had  an  attack  of  vomiting,  which  lasted  for  two 
months. 

On  November  19,  1914,  x-ray  treatment  was  begun  and  con- 
tinued once  a  week  for  about  two  months. 

Physical  examination,  upon  admission  to  the  General  Mem- 
orial Hospital,  March,  191 5,  showed  a  mass  in  the  left  cervical 
region,  consisting  of  two  nodules  (2  cm.  in  diameter),  slightly 
tender  and  freely  movable.  No  glands  could  be  felt  in  the 
abdomen.  The  largest  tumor,  situated  in  the  right  inguinal 
region,  measured  6  cm.  in  diameter;  was  flat  on  the  surface 
and  more  deeply  fixed  than  the  other  tumors.  Three  small 
nodules  the  size  of  a  hickory  nut  were  situated  in  the  left  thigh 
and  four  more  in  the  right  thigh.  Knee-jerks  exaggerated.  The 
patient  stated  that  she  had  had  for  some  time  what  she  char- 
acterized as  "rheumatic  or  grip  attacks"  twice  a  week,  accom- 
panied by  muscular  pains  and  general  malaise.  She  had  noticed 
that  almost  immediately  after  each  one  of  these  so-called  "at- 
tacks of  grip"  a  new  nodule  appeared.  Blood  test  made  showed: 
White-blood  cells,  7500;  polynuclears,  71  per  cent.;  eosino- 
philes,  4  per  cent.;  transitionals,  11  per  cent.;  lymphocytes,  3 
per  cent.  A  large  amount  of  nuclears,  11  per  cent.  Wassermann 
negative. 


56  coley:  neoplasms  of  the  lymphatic  glands 

The  toxins  were  begun  April  10,  in  0.5  minim  doses  and 
gradually  increased  up  to  12  minims;  she  received  in  all  twenty 
four  injections  while  in  the  hospital.  During  the  treatment 
the  nodules  became  much  smaller,  and  after  leaving  the  hospital 
some  of  them  entirely  disappeared. 

The  patient  was  again  admitted  to  the  General  Memorial 
Hospital  on  October  9,  191 5,  and  stated  that  in  the  meantime 
nearly  all  of  the  nodules  had  entirely  disappeared,  but  that  a 
few  weeks  ago  she  began  to  have  great  pain  in  the  back,  and 
throughout  the  right  iliac  region. 

Physical  examination  at  this  time  shows  tenderness  in  the 
region  between  the  scapula  and  the  vertebral  hne  on  the  left 
side.  An  enlarged  gland  can  be  seen  in  the  axilla,  and  there  is 
dulness  in  the  retroperitoneal  region,  over  an  area  of  two  and 
a  half  inches.  The  inguinal  glands  are  not  enlarged,  and  no 
enlargement  can  be  felt  in  the  abdomen. 

In  the  right  thigh  there  is  some  pain  and  tenderness,  also  in 
the  sacral  region;  pelvic  examination  negative.  The  tumors 
that  were  present  at  the  time  of  her  first  admission  to  the  hospital 
have  practically  all  disappeared. 

November  18.  The  patient's  general  condition  has  become 
worse,  and  there  is  evidence  of  spinal  involvement. 

V. — sarcoma  op  retroperitoneal  and  mesenteric  glands 

Case  XXVIII. — Intra-abdominal  lymphosarcoma,  involving 
mesentery,  mesenteric  glands  and  portion  of  small  intestine. 

Mrs.  W.,  aged  twenty-five  years,  was  operated  upon  in  Novem- 
ber, 1 9 13,  by  Dr.  Wilham  M.  Conant,  of  the  Massachusetts 
General  Hospital,  for  an  abdominal  tumor.  Exploratory  opera- 
tion showed  a  tumor  the  size  of  a  closed  fist,  occupying  the 
posterior  parietal  part  of  the  mesentery  and  a  portion  of  the  small 
intestine.  It  was  so  extensive  that  no  attempt  was  made  to 
remove  it.  A  portion  was  excised  for  microscopic  examina- 
tion, which  was  made  by  Dr.  W.  F.  Whitney  and  Dr.  A.  C. 
Potter  the  former  the  pathologist  of  the  Massachusetts  General 


coley:  neoplasms  of  the  lymphatic  glands  57 

Hospital,  the  latter  of  the  Harvard  Medical  School — who  pro- 
nounced it  round-celled  sarcoma.  In  December,  1903  the 
patient  was  referred  to  me  by  Dr.  Conant  and  I  immediately 
put  her  upon  the  mixed  toxins,  giving  five  to  six  injections  a 
week,  also  adding  the  number  of  :r-ray  treatments.  The  tumor 
immediately  began  to  decrease  in  size  and  at  the  end  of  four 
months  it  had  entirely  disappeared.  At  this  time  the  patient 
developed  a  high  temperature  and  acute  abdominal  symptom, 
pointing  to  a  local  peritonitis,  due — as  it  proved — to  a  necrosed 
portion  of  the  small  intestine  involved  in  the  tumor.  She  was 
desperately  ill  and  hope  of  life  was  abandoned  for  more  than  a 
week.  Thereupon  a  fecal  fistula  developed  and  she  slowly 
recovered  her  health.  She  ran  irregular  temperatures  until  the 
latter  part  of  July,  when  the  temperature  fell  to  normal.  The 
toxins  were  given  for  a  considerable  time  after  recovery  by 
her  family  physician.  Dr.  William  Wilson,  of  Pawtucket,  R.  I. 
In  a  letter  received  from  Dr.  Wilson,  dated  February  13,  1906, 
he  stated  that  evidence  of  a  return  had  appeared  in  the  spring  of 
1905,  as  shown  by  accumulation  of  fluid  in  the  peritoneal  cavity. 
Dr.  Conant  was  called  in  and  estabhshed  permanent  drainage; 
at  which  time  he  discovered  several  retroperitoneal  growths. 
The  condition  gradually  became  worse  and  the  patient  died  a 
few  months  later. 

Case  XXIX. — Round-celled  sarcoma  of  mesentery  and  small 
intestine. 

J.  B.,  physician,  aged  fifty-six  years;  noticed  a  rapidly 
growing  tumor  in  the  lower  portion  of  the  abdomen  just  above 
the  bladder  in  the  summer  of  1904.  Operation  by  Dr.  J.  S. 
Mixter  in  September,  1904,  when  the  growth  had  reached  the 
size  of  two  fists.  The  disease  was  pronounced  to  be  round-celled 
sarcoma,  probably  originating  in  the  mesenteric  glands. 

As  all  of  the  tumor  could  not  be  removed,  the  ic-rays  plus 
mixed  toxins  of  erysipelas  and  Bacillus  prodigiosus  were  begun 
ten  days  after  operation  and  continued  for  two  months.  The 
induration  disappeared  and  the  patient  remained  well  until 
the  spring  of  1907,  two  and  a  half  years,  when  a  local  recur- 


58  coley:  neoplasms  of  the  lymphatic  glands 

rence  occurred  in  the  lower  portion  of  the  abdomen.  A  central 
mass  the  size  of  two  fists  and  several  outlying  smaller  ones  could 
be  made  out  on  palpation.  The  mixed  toxins  were  again  given  by 
Dr.  Mixter  and  the  tumors  diminished  rapidly  in  size.  During 
the  month  of  May  the  size  of  the  dose  was  reduced  with  the 
result  that  the  tumor  again  began  to  increase.  The  patient 
was  then  placed  under  my  care  for  six  weeks  but,  on  account 
of  the  severe  local  reactions  following  the  injections,  was  unable 
to  take  more  than  4  to  5  minims  at  a  dose;  he  was  further- 
more suffering  from  indigestion  and  had  very  little  appetite,  so 
that  the  treatment  could  not  be  pushed  as  far  as  desirable. 
Nevertheless,  the  disease  was  held  in  check  until  November, 
1907,  when  a  second  operation  was  performed  by  Dr.  Mixter, 
which,  however,  was  a  partial  one  only,  although  a  portion  of 
tumor  weighing  four  and  a  half  po\mds  was  removed.  The 
patient  made  a  good  recovery  and  after  two  weeks  the  toxin 
treatment  was  resumed.  His  appetite  improved  greatly  and  on 
December  7  his  general  condition  seemed  better  than  for  a 
year,  he  having  gained  twelve  pounds  since  the  operation.  In 
view  of  the  good  condition  Dr.  Mixter  believed  it  possible  to 
remove  the  remaining  portion  of  the  tumor  and  performed  a 
third  operation  which  proved  fatal,  the  patient  dying  from  shock. 

Case  XXX. — Sarcoma  intra-abdominal  involving  omentum, 
mesentery  of  small  intestine,  and  gall  bladder. 

E.  J.,  female,  aged  twenty-three  years.  In  1894  she  began  to 
have  attacks  of  pain  in  the  right  hypochondriac  region,  which 
gradually  became  more  frequent  and  severe,  with  depreciation 
of  general  health  until  finally  she  was  confined  to  bed.  August 
16,  1894,  exploratory  operation  by  Dr.  Willy  Meyer  of  New 
York.  A  solid  tumor  was  found  apparently  springing  from  the 
mesentery  of  the  intestine  and  attached  to  omentum  and  gall- 
bladder. It  was  clearly  inoperable  and  no  attempt  was  made 
to  remove  it;  a  portion  was  excised  for  microscopic  examina- 
tion and  the  abdomen  closed.  The  examination  of  the  piece 
removed  was  made  by  the  pathologist  of  the  German  Hospital, 
Dr.  F.  Schwyzer,  who  pronounced  it  round-celled  sarcoma. 


coley:  neoplasms  of  the  lymphatic  glands  59 

Early  in  1894,  as  soon  as  the  patient  recovered  from  the 
operation.  Dr.  Meyer  referred  her  to  me  for  the  toxin  treatment. 
Palpation  at  this  time  showed  and  intra-abdominal  mass  beneath 
the  cicatrix  in  the  right  hypochondrium,  about  four  inches  in 
diameter;  the  tumor  was  hard  and  fLxed.  General  condition 
good.  Systemic  treatment  with  the  mixed  toxins  was  begun, 
the  injections  being  given  alternately  in  the  abdominal  wall 
and  buttocks.  They  were  kept  up,  with  occasional  intervals  of 
rest,  until  February  7,  1895,  five  months,  with  the  result  that 
the  tumor  gradually  disappeared.  The  patient  was  in  good 
health  and  free  from  recurrence,  twelve  years  later  since,  which 
time  I  have  lost  sight  of  her. 

Case  XXXI. — Inoperable  spindle-celled  sarcoma  of  the  retro- 
peritoneal region  and  iliac  fossa  clinical  diagnosis.  Disappear- 
ance under  the  toxins.     Well  three  and  a  half  years  later. 

J.  G.  K.,  male,  aged  twenty-five  years.  In  December,  191 1, 
first  noticed  swelhng  just  above  the  crest  of  the  ilium  on  the  right 
side.  This  gradually  increased  in  size  but  there  was  no  pain; 
no  swelling  in  leg ;  slight  loss  of  weight.  The  patient  was  referred 
to  me,  March  26,  191 2,  by  Dr.  E.  W.  Hedges,  of  Plainfield,  N. 
J.,  and  Dr.  John  L.  Erdman  later  pronounced  the  disease  sar- 
coma and  inoperable.  Physical  examination  at  this  time 
showed  a  tumor  behind  the  right  inguinal  and  iliac  region, 
extending  down  over  the  crest  of  the  ilium,  but  not  into  Scarpa's 
triangle,  and  upward  about  three  inches.  It  apparently  had 
its  origin  in  the  retroperitoneal  region  or  anterior  surface  of  the 
ilium;  the  skin  was  not  involved.  The  tumor  was  soft  and  semi- 
fluctuating  with  small  areas  almost  nodular  in  character.  Aspira- 
tion at  various  times  showed  only  bloody  serum. 

The  patient  had  been  examined  by  Dr.  John  L.  Erdman, 
New  York  City,  who  believed  the  trouble  to  be  of  malignant 
nature  and  inoperable.  He  was  admitted  to  Dr.  Bull's  Private 
Hospital  where  the  treatment  with  the  mixed  toxins  was  started 
and  continued  for  two  months.  At  the  end  of  four  weeks  the 
tumor  became  distinctly  fluctuating,  and  under  ether  I  made 
incision  just  above  the  upper  part  of  the  ilium,  and  evacuated 


6o  coley:  neoplasms  of  the  lymphatic  glands 

several  ounces  of  fluid,  with  a  large  amount  of  necrotic  material 
resembling  broken-down  sarcoma. 

Although  the  material  was  too  badly  degenerated  to  make 
satisfactory  section,  Dr.   Ewing's  report  states: 

"The  sections  show  a  process  which  is  either  very  closely 
related  to,  or  identical  with,  sarcoma.  It  is  made  up  chiefly 
of  granulation  tissue,  spindle  cells  and  giant  cells.  Much  of 
it  is  necrotic.     The  process  shows  no  signs  of  tubercle." 

Although  not  entirely  positive.  Dr.  Ewing's  report,  together 
with  the  chnical  history,  leaves  little  doubt,  I  think,  as  to  the 
dia,gnosis. 

November  i,  191 5.  The  patient  is  still  in  good  health,  but  a 
small  sinus  persists.^ 

Case  XXXII. — Sarcoma  of  the  mesentery. 

Mrs.  M.,  always  in  good  health  up  to  the  beginning  of  Jan- 
uary, 1914,  when  she  noticed  a  lump  in  the  abdominal  cavity. 
This  continued  to  increase  rapidly  in  size  and  was  operated 
upon  in  April  a  mass  the  size  of  a  child's  head  was  removed. 
Microscopic  examination  showed  it  to  be  a  spindle-celled  sar- 
coma. This  diagnosis  was  confirmed  by  Dr.  S.  T.  Graves,  of 
Chicago. 

The  tumor  promptly  recurred,  and  in  August,  1914,  a  similar 
growth  of  nearly  the  same  size  was  removed.  The  tumor  was 
found  to  be  attached  to  the  mesentery  and  the  operation  was  re- 
garded as  an  incomplete  one.  The  patient  was  referred  to  me  for 
the  toxin  treatment  and  admitted  to  the  General  Memorial  Hos- 
pital on  September  15,  1914.  The  toxins  were  given  chiefly  in  the 
buttocks,  the  initial  dose  being  0.5  minim;  this  was  gradually 
carried  up  to  7  minims,  which  latter  produced  a  temperature  of 
104.5°.  During  her  stay  in  the  hospital  she  received  two  :r-ray 
treatments,  one  on  September  18,  another  on  October  8.  She 
left  the  hospital  on  October  12,  and  after  that  received  three 
treatments  a  week  at  my  office  for  two  months,  in  doses  not  suffi- 

1  The  sinus  was  curetted  by  his  family  physician  Nov.  16,  1915,  and  the 
tissue  submitted  to  a  pathologist  who  made  the  diagnosis  of  "Mild  form 
of  tuberculosis,  based  on  guinea-pig  inoculation."  I  do  not  regard  this  as 
any  evidence  that  the  original  trouble  was  tuberculous.  The  clinical  and 
microscopic  evidence  was  strongly  against  it. 


coley:  neoplasms  of  the  lymphatic  glands  6 1 

cient  to  caused  any  marked  reaction.  No  evidence  of  recurrence 
developed  and  the  patient  returned  to  her  home  in  the  Wesi, 
where  she  had  the  treatment  continued  by  her  local  physician 
until  August  15,  1915.  Her  general  health  has  remained  good 
and  at  the  present  time  there  is  no  evidence  of  a  recurrence. 
The  treatment  has  been  discontinued. 

With  reference  to  the  histological  classification  of  the  tumor  in 
this  case,  Dr.  Graves  stated: 

"Several  of  our  best  pathologists  examined  the  specimens 
and  confirmed  my  diagnosis  of  sarcoma,  but  we  all  agreed 
upon  the  point  that  from  microscopic  findings  alone,  without 
consideration  of  the  clinical  history  and  gross  findings  at  opera- 
tions, there  would  be  doubt  as  to  whether  the  tumor  was  a  fibroma 
of  a  malignant  type." 

Dr.  Wilham  H.  Welch's  report  on  the  case,  made  December 
17,  1914,  reads  as  follows: 

"The  microscopic  sections  show  a  new  growth  composed  of 
fibrillated  connective  tissue,  fairly  rich  in  cells  and  containing 
a  good  supply  of  bloodvessels.  The  cells  appear  mostly  as 
fusiform  and  branching  iibroblasts.  The  basement  substance 
is  for  the  most  part  rather  delicately  fibrillated  even  in  places 
rather  mucoid  in  character,  but  in  some  areas  it  is  more  coarsely 
fibrous.  It  appears  to  grow  some  time  in  a  definite  relation  to 
the  bloodvessels,  but  this  is  not  everywhere  noticeable.  The 
cells  are  in  good  number,  but  hardly  so  abundant  as  to  warrant 
the  diagnosis  of  sarcoma,  although  the  distinction  is  often  a 
matter  of  individual  opinion.  There  are  no  glandular  elements 
in  the  section  on  lymphatic  tissue,  so  that  the  origin  of  the 
tumor  cannot  be  determined,  other  than  that  from  connective 
tissue.     Diagnosis:     fibroma." 

Dr.  James  Ewing  reported : 

"The  tumor  is  a  rather  cellular  myxomatous  fibroma.  Struct- 
ure suggests  it  to  be  of  neural  origin.  Probably  possesses  only 
a  local  malignancy." 


62  coley:  neoplasms  of  the  lymphatic  glands 


VII. — SARCOMA   OF   MEDIASTINAL   GLANDS 

Case  XXXIII. — Sarcoma  of  the  mediastinal  glands.  Clinical 
and  x-ray  diagnosis. 

G.  B.,  male,  aged  fifty- three  years,  referred  to  me  by  Dr.  G. 
R.  Butler,  of  Brooklyn,  on  November  25,  1908,  for  what  was 
believed  to  be  a  malignant  tumor  of  the  mediastinum.  There 
was  no  family  or  personal  history  of  tuberculosis;  no  history  of 
syphilis.  He  had  first  noticed  huskiness  of  voice  fifteen  months 
before,  which  gradually  increased;  some  dyspnea,  which  slowly 
became  more  pronounced.  Physical  examination  on  November 
25,  1908,  showed  dulness  over  the  whole  mediastinum;  the 
abdomen  was  distended,  some  ascitic  fluid  being  present.  No 
swelling  of  feet  and  hands.  General  condition  good;  no  loss 
of  weight.  Just  above  the  clavicle  and  attached  to  the  sterno- 
clavicular portion  of  the  sternomastoid  muscle  there  was  a  small, 
hard  gland.  No  enlargement  of  thyroid.  A  careful  :r-ray 
examination  made  by  Dr.  Charles  Eastmond,  of  Brooklyn,  on 
September  29,  1908,  showed  a  large  tumor  occupying  the 
mediastinal  region.  The  patient  was  immediately  put  upon  the 
mixed  toxins  which  were  given  under  my  direction. 

A  second  ;r-ray  examination  made  December  31,  1908,  showed 
some  diminution  in  the  size  of  the  tumor.  The  toxins  were 
continued  for  one  and  a  half  years  with  occasional  intervals 
of  rest.  X-ray  examinations  made  from  time  to  time  showed 
a  slow,  but  continued  diminution  in  the  size  of  the  tumor  with 
decrease  in  density,. 

Examination  of  the  patient  made  March  13,  191 1,  two  and 
a  half  years  afterward,  showed  his  general  condition  perfectly 
normal;  the  hoarseness  had  remained  about  the  same;  the 
dulness  had  markedly  decreased.  X-ray  examination  showed 
a  decrease  in  size  and  density  of  the  tumor. 

When  I  last  examined  the  patient,  in  the  latter  part  of  October, 
1914,  he  was  in  good  health,  more  than  six  years  after  the  treat- 
ment was  begun. 


coley:  neoplasms  of  the  lymphatic  glands  63 

The  next  group  of  cases  illustrates  the  difficulties  in  render- 
ing a  definite  histological  diagnosis  in  neoplasms  of  the  lymphatic 
glands: 

Borderline  Cases  with  Clinical  Diagnosis  of  Hodgkin's  Disease, 
Microscopic  Diagnosis  of  Sarcoma,  or  Vice  Versa 

Case  XXXIV. — Small  round-celled  sarcoma  of  neck;  clinically 
Hodgkin's  disease. 

L.  B.  J.,  male,  aged  thirty-one  years,  clergyman,  came  under 
my  care  on  June  22,  1908.  Three  years  before  he  had  noticed 
a  lump  in  the  neck  on  a  Thursday,  for  which  he  consulted  a 
physician  on  Friday,  and  by  Saturday  it  had  increased  so  much 
that  he  was  unable  to  get  on  his  collar.  On  the  following  Monday, 
February  7,  1905,  or  four  days  after  he  first  noticed  the  swelling 
he  consulted  Dr.  Tinker,  of  Ithaca,  who  did  a  complete  block 
dissection  a  few  days  later,  after  which  the  patient  remained 
free  from  trouble  until  November,  1907,  when  there  was  a 
local  recurrence  for  which  a  secondary  operation  was  done  by 
Dr.  Tinker.  The  patient's  general  health  and  strength  became 
deteriorated  and  other  glands  appeared  in  the  neck,  axillae, 
and  groins.  In  March,  1908,  a  third  operation  was  done,  fol- 
lowed immediately  by  daily  x-rsLy  treatment  for  ten  weeks. 
Microscopic  examination  by  Dr.  Nicholson,  of  the  Clifton 
Springs  Sanatorium,  showed  the  disease  small  round-celled  sar- 
coma. 

On  June  22,  1908,  the  patient  was  referred  to  me  by  Dr. 
Tinker.  Physical  examination  at  this  time  showed  the  patient 
markedly  emaciated  (his  weight  had  fallen  from  one  hundred 
and  sixty  pounds  to  one  hundred  and  forty- three  and  a  half 
pounds).  There  were  very  extensive  scars  in  both  sides  of 
the  neck  and  the  supracla'vicular  region.  There  were  two  to 
three  small  nodules  the  size  of  a  pea  in  the  cervical  region,  but 
no  local  recurrence;  no  glands  in  the  axillae;  slightly  enlarged 
glands  in  the  groin;  spleen  not  enlarged,  but  liver  markedly  so; 
no  ascites.     Pulse,  140;    temperature,  normal.     The  glandular 


64  coley:  neoplasms  of  the  lymphatic  glands 

tumors  had  evidently  been  very  markedly  diminished  by  the 
previous  x-ray  treatment.  The  patient's  general  condition  was 
so  bad  that  it  was  not  thought  wise  to  give  him  the  toxins. 
The  disease  progressed  rapidly  and  he  died  on  September  i, 
1908. 

The  tumor  in  this  case,  while  clinically  Hodgkin's  disease, 
was  pronounced,  microscopically,  small  round-celled  sarcoma. 

Case  XXXV. — Lymphosarcoma  on  neck,  or  Hodgkin's  disease. 

E.  J.,  son  of  the  preceding  case,  aged  seven  and  a  half  years. 
Personal  history:  Rather  sickly  since  birth;  had  measles  in  Feb- 
ruary, 191 1,  shortly  after  which  enlarged  glands  were  noticed  in 
both  sides  of  the  neck;  two  months  later  similar  enlargements  ap- 
peared in  both  axillary  and  inguinal  regions.  One  of  the  tumors 
was  excised  by  Dr.  Coultas,  of  Chatham,  N.  J.,  and  pronounced 
sarcoma  by  the  pathological  department  of  the  College  of  Phy- 
sicians and  Surgeons.  Upon  my  advice  the  patient  was  put 
upon  the  mixed  toxin  treatment  which  was  carried  out  two  or 
three  times  a  week  by  Dr.  Coultas,  steady  subsidence  of  the 
tumors  following.  At  the  end  of  three  months  an  interval  of 
rest  was  allowed,  whereupon  the  glands  began  to  enlarge  again. 
The  treatment  was  resumed  and  pushed  to  the  point  of  producing 
rather  severe  reactions;  the  tumors  soon  began  to  decrease  in 
size  again  and  finally  disappeared  entirely.  Physical  examina- 
tion by  me  on  June  10,  191 2,  nearly  one  year  after  the  beginning 
of  the  treatment,  showed  the  patient  in  good  physical  condition ; 
no  enlargement  of  glands  was  noticeable  on  inspection,  but 
palpation  showed  in  the  right  cervical  region  5  very  small 
nodules,  beginning  just  above  the  clavicle  behind  the  sterno- 
mastoid  muscle,  ranging  in  size  from  a  buckshot  to  a  pea.  A 
similar  condition  was  found  on  the  left  side,  although  the  glands 
were  smaller  in  size.  Just  behind  the  ear,  over  the  mastoid, 
was  a  larger  gland,  about  the  size  of  a  bean,  not  adherent  to  bone 
or  skin.  No  glands  could  be  felt  in  axillae  or  groins  and  there 
was  no  enlargement  of  spleen  or  liver.  The  patient  remained 
in  good  health  until  the  end  of  March  1914,  when  the  glandular 
tumors  seemed  to  be  increasing  in  size  and  he  was  admitted  to 


coley:  neoplasms  of  the  lymphatic  glands  65 

my  service  at  the  Hospital  for  Ruptured  and  Crippled.  He 
was  again  put  upon  the  mixed  toxin  treatment,  receiving  thirty- 
six  injections  in  all  between  April  i  and  July  18.  One  of  the 
small  glands  was  removed  and  examined  by  Dr.  James  Ewing, 
who  found  no  evidence  of  malignancy.  The  pathological^  report 
at  the  Hospital  for  Ruptured  and  Crippled  stated  epithelio- 
sarcoma.  Under  the  toxins  the  various  glandular  tumors  again 
subsided,  and  the  patient  was  discharged  on  July  18,  1914. 

In  view  of  his  very  much  hj^ertrophied  tonsils,  it  was 
thought  possible  that  the  tonsils  were  the  source  of  infection, 
and  I  referred  him  to  the  Manhattan  Ear  and  Eye  Hospital, 
where  his  tonsils  were  removed  by  Dr.  Monroe.  A  very  careful 
bacteriological  and  microscopic  study  was  made  by  both  Dr. 
Ewing  at  the  Cornell  Laboratory,  and  at  the  laboratory  of  the 
Manhattan  Eye  and  Ear  Hospital,  and  no  diphtheroid  bacilli 
were  found,  nor  any  evidence  of  malignancy.  The  boy  was 
examined  by  Dr.  William  L.  Culbert  on  July  i,  191 5,  and  found 
in  good  health,  four  years  after  the  treatment  was  begun  now 
December  5,  1915. 

Here,  again,  we  have  a  case  of  typical  Hodgkin's  disease, 
clinically,  which  was  pronounced  sarcoma  on  microscopic 
examination. 

Case  XXXVI. — Lymphosarcoma  of  Neck,  or  Hodgkin's  disease. 

Miss  S.  K.,  aged  fifty-five  years,  was  referred  to  me  in  Decem- 
ber, 1913,  by  Dr.  Arpad  G.  Gerster,  with  the  following  history: 
A  tumor  was  removed  from  the  right  side  of  her  neck  at  Gouver- 
neur  Hospital  nine  years  before.  In  March,  1913,  a  second  opera- 
tion was  performed  by  Dr.  Erdman  for  a  local  recurrence;  the 
tumor  removed  weighed  three-fourths  pound,  and  was  pronounced 
lymphosarcoma  by  the  pathological  department  of  Bellevue  Hos- 
pital. The.  tumor  again  recurred  in  the  fall  of  1913,  and  the 
patient  was  then  referred  to  me  by  Dr.  Gerster  as  an  inoperable 
case.  Physical  examination  at  this  time  (December,  19 13) 
showed  several  tumors  occupying  the  right  cervical  region 
between  the  mastoid  and  clavicle,  varying  in  size  from  a  hickory 
nut  to  a  hen's  egg.     The  tumors  were  smooth  in  outline,  freely 


66  coley:  neoplasms  of  the  lymphatic  glands 

movable,  more  or  less  discrete;  skin  not  adherent;  consistence 
only  moderately  firm;  no  glands  in  either  axilla  or  groin.  No 
enlargement  of  spleen  or  liver.  The  patient  was  put  upon  the 
mixed  toxins  of  erysipelas  and  Bacillus  prodigiosus.  She  proved 
very  susceptible,  the  highest  dose  given  being  5  minims.  After 
fifteen  treatments,  the  tumors  had  diminished  markedly  in 
size  and  became  more  freely  movable,  so  that  I  believed  it  wise 


Fig.  30. — Case  XXXVI.     Lymphosarcoma;     one    laboratory.     Hodgkin's 
disease.      (Ewing.) 


to  attempt  their  removal  by  operation.  This  was  done  by  my 
associate,  Dr.  William  A.  Downes,  on  January  15,  1914.  Dr. 
Swing's  report  on  the  specimen,  dated  January  15,  1914,  read: 
''Typical  Hodgkin's  disease;  granuloma;  giant  cells;  hyaline 
and  fibrin  areas." 

The  disease  recurred  shortly  after  the  operation  and  grew 
more  rapidly  than  before.  She  was  then  put  upon  a^-ray  treat- 
ment, under  which  there  was  marked  diminution  in  the  size  of 


coley:  neoplasms  of  the  lymphatic  glands 


67 


the  tumor  which,  however,  proved  temporary  only.  Her  later 
history  we  have  been  unable  to  trace. 

Case  XXXVII. — Lymphosarcoma  of  the  neck,  clinical  diagnosis; 
microscopic  examination;  round-celled  sarcoma,  one  report;  atypical 
Hodgkin's  disease,  another. 

J.  J.  D.,  male,  referred  to  me  by  Dr.  William  H.  Bishop,  on 
November  6,  1913,  with  a  history  of  having  had  cirrhosis  of 


Fig.  31. — Case  XXXVII.     One    pathologist    pronounced    specimen    round- 
celled  sarcoma;  another  reported  atypical  Hodgkin-'s  disease. 


liver  five  years  ago  accompanied  by  a  severe  attack  of  jaundice. 
Sixteen  months  ago  he  first  noticed  a  small  lump  in  the  left 
cervical  region  just  anterior  to  the  sternomastoid  muscle;  no 
pain  nor  tenderness.  The  tumor  slowly  increased  in  size  until 
October,  191 2,  when  he  was  operated  upon  by  Dr.  Bishop;  no 
microscopic  examination  of  the  specimen  was  made  at  that 
time.  In  May,  19 13,  there  was  a  rapidly  growing  recurrent 
growth   with   involvement   of   the   supraclavicular   glands.      A 


68  coley:  neoplasms  of  the  lymphatic  glands 

second  extensive  operation  was  performed  by  Dr.  Bishop  at  the 
end  of  September,  1913.  Two  weeks  later  a  recurrence  was 
notice  in  the  upper  part  of  the  scar,  which  grew  rapidly  in  size 
in  spite  of  x-ray  treatment. 

On  November  6,  1913,  the  patient  was  referred  to  me  by 
Dr.  Bishop  for  the  toxin  treatment.  He  had  then  just  recov- 
ered from  a  recent  attack  of  jaundice.  The  report  of  the  micro- 
scopic examination  made  by  Dr.  Louis  Heitzmann,  of  the  tumor 
removed  at  the  second  operation,  read:  "Hypertrophy  with 
lymphadenoma,  changing  into  myxolymphosarcoma;  small  and 
large  round  cells." 

The  toxins  were  given  four  to  five  times  a  week,  and  at  first 
there  was  slight  diminution  in  the  size  of  the  tumor;  later, 
however,  the  treatment  apparently  had  little  effect.  On  Jan- 
uary 7,  1 9 14,  a  third  and  very  radical  operation  was  performed 
by  Dr.  Bishop  (assisted  by  me)  consisting  in  a  complete  block 
dissection  of  the  cervical  glands  from  mastoid  to  sternum.  The 
largest  mass  was  situated  near  the  upper  cervical  region,  just 
under  the  sternomastoid  muscle  and  continued  through  another 
group  of  infiltrated  glands  which  extended  forward  involving 
the  submaxillary  glands.  The  whole  sternomastoid  muscle  was 
removed  and  all  of  the  external  fascia  including  about  four  inches 
of  the  internal  jugular  vein.  The  wound  was  fulgurated  for 
eight  minutes  with  the  Keating-Hart  apparatus.  The  toxins 
were  resumed  at  the  end  of  one  week.  The  specimen  removed 
at  this  operation  was  examined  by  Dr.  James  Ewing,  who 
pronounced  the  disease  (atypical)  Hodgkin's  disease. 

One  month  later  in  spite  of  continued  toxin  treatment,  there 
was  evidence  of  a  local  recurrence,  forming  more  of  an  infiltration 
of  the  whole  neck,  than  a  distinct  localized  tumor. 

On  April  20  there  was  a  well-marked  recurrence  in  the  supra- 
clavicular and  mid-cervical  regions.  A  gland  the  size  of  a  hazel- 
nut was  palpable  in  the  anterior  cervical  region,  two  inches 
above  the  clavicle  on  the  right  side  and  another  mass  on  the  left 
side.  He  was  then  given  a  trial  with  the  mixed  toxins  of  the 
Staphylococcus  aureus   and  Bacillus  prodigiosus  under  which 


coley:  neoplasms  of  the  lymphatic  glands  69 

treatment  he  showed  some  improvement  at  first.  I  then  gave 
him  the  vaccine  of  the  diphtheroid  bacillus  removed  from 
another  case  of  mine.  There  was  steady  decrease  in  the  size 
of  the  tumors,  and  rehef  from  pain  which  had  already  become 
constant  and  rather  severe;  his  weight  also  began  to  increase. 
The  improvement  was  only  temporary,  however,  and  on  May 
9  it  was  thought  best  to  discontinue  the  treatment.  He  "died 
suddenly,  as  a  result  of  a  cerebral  hemorrhage,  on  June  8,  1914. 
Tne  clinical  features  of  the  disease  were  characteristic  of  sarcoma 
rather  than  Hodgkin's. 

Case  XXXVIII. — Lymphosarcoma  of  tonsil  and  neck  with 
metastases  in  the  abdomen  (resembling  a  typical  Hodgkins  or 
leukemia) . 

J.  Z.,  male,  aged  twenty-nine  years.  In  the  fall  of  1913,  during 
an  attack  of  tonsillitis  he  noticed  a  swelling  on  the  right  side 
of  the  neck  accompanied  by  some  pain.  The  swelling  subsided 
and  returned  three  times.  He  entered  the  New  York  Hospital 
early  in  April,  19 14,  and  Dr.  Eugene  Pool  removed  one  of  the 
glands  of  the  neck  for  microscopic  examination.  The  patho- 
logical diagnosis  made  by  Dr.  Elser  read:  "probably  lympho- 
sarcoma." The  patient  had  lost  about  twenty  pounds  in  weight. 
On  April  30,  Dr.  Pool  referred  him  to  me  for  the  toxin  treatment. 
Physical  examination  at  this  time  showed  the  whole  right 
supraclavicular  and  cervical  region  occupied  by  a  tumor  about 
the  size  of  two  fists,  extending  nearly  to  the  chin  in  front  and  the 
vertebral  line  behind;  the  skin  was  normal  in  appearance  and 
the  tumor  smooth  in  outline;  axillary  and  inguinal  glands  were 
enlarged.  The  left  side  was  occupied  by  a  similar  mass  which, 
however,  was  not  so  extensive  as  on  the  right  side.  A  large 
tumor  was  found  in  the  right  tonsil.  This  was  probably  the 
primary  growth,  while  the  tumors  of  the  neck  were  secondary. 
He  was  admitted  to  the  General  Memorial  Hospital;  weight 
on  entrance  was  one  hundred  and  twenty-eight  pounds. 

Blood  examinations  showed  on  March  10,  1914:  White-blood 
cells,  4800;  polynuclears,  42  per  cent.;  mononuclears,  56  per 
cent.;    eosinophiles,  2  per  cent. 


70  coley:  neoplasms  of  the  lymphatic  glands 

April  29,  1 9 14:  White-blood  cells,  2000;  hemoglobin,  50 
per  cent. 

May  24,  1914:  White-blood  cells,  4000;  hemoglobin,  64  per 
cent.;    polynuclears,  25  per  cent.;    mononuclears,  75  per  cent. 

The  patient  was  treated  with  the  killed  cultures  of  the  Staphyl- 
ococcus aureus,  of  which  he  received  nine  doses,  starting  with 
I  minim  and  carried  up  to  15  minims,  which  produced  a  tem- 
perature of  99°  to  102.°  This,  however,  had  practically  no 
effect  upon  the  progress  of  the  disease,  and  a  few  doses  of  the 
mixed  toxins  of  erysipelas  and  Bacillus  prodigiosus  were  given 
but  were  not  carried  up  to  the  point  of  producing  a  moderate 
reaction.  The  patient's  general  condition  failed  so  rapidly  that 
no  further  treatment  was  tried.  He  continued  to  lose  in  flesh  and 
strength,  and  died  on  June  18,  1914,  about  fifty  days  after  he 
had  entered  the  hospital,  or  eight  months  after  the  beginning 
of  the  disGiase. 

On  May  21  a  small  gland  was  removed  and  examined  by  Dr. 
Ewing,  who  reported: 

"Lymph  nodes.  Various  nodes  show  mild  overgrowth  of 
lymphocytes,  resembling  Hodgkin's  but  without  giant  cells. 
The  proliferation  is  less  active  than  in  leukemia  but  much  less 
active  than  in  lymphosarcoma.  In  some  nodes  the  vessels  are 
very  abundant.     In  others  there  is  beginning  fibrosis. 

"Spleen:    Atrophy  of  lymphoid  cells;    much  fibrosis. 

"  Epicritical :  This  case  unites  some  of  the  features  of  Hodg- 
kin's, pseudoleukemia,  and  leukemia.  The  lymph  nodes  are 
most  like  atypical  Hodgkin's.  The  liver  lesions  are  indistinguish- 
able from  those  of  pseudoleukemia,  and  the  excess  of  leukocytes 
in  the  vessels  suggests  that  there  was  a  terminal  leukemia." 

This  is  one  of  the  few  cases  in  which  it  was  possible  to  get  a 
full  autopsy,  which  was  made  by  Dr.  Ewing,  whose  report  I 
believe  will  be  of  interest: 

Autopsy  Report  (June  19,  19 14). 

Body:    Much  emaciated,  slightly  jaundiced. 

Heart:  There  are  three  subpericardial  fiat  tumors  along  the 
anterior  coronary  artery.    Heart  otherwise  normal. 


coley:  neoplasms  of  the  lymphatic  glands  71 

Lungs:  Show  intense  congestion  and  edema  of  left  lung. 
Fresh  pleurisy  over  right  lung.  Bronchial  lymph  nodes  rauch 
enlarged.  Acute  lobar  pneumonia  upper  lobe,  one  metastatic 
nodule  in  central  part.     One  supernumerary  spleen. 

Spleen:  Much  enlarged  20  cm.  by  10  cm.  by  5  cm.  Uniformly 
pale,  congested,  cellular. 

Liver:  Moderately  enlarged,  slightly  nutmeg  on  section. 
Lobules  seem  oversized. 

Kidneys:  Left  kidney  much  enlarged.  Cortex  thick,  pale, 
markings  indistinct.  Right  kidney  missing  and  right  ureter 
missing.  Inguinal,  lumbar,  mesenteric,  thoracic  lymph  nodes 
moderately  enlarged. 

Stomach:    Pale  but  normal. 

Bladder  and  Prostate:    Normal. 

Rectum:  Normal.  Lower  Peyer's  patches  normal.  Region 
of  mediastinum  is  seat  of  large  firm  tumor  mass,  continues  with 
cervical  tumors.  Follicles  at  base  of  tongue  slightly  enlarged. 
Tumors  of  neck  considerably  compress  trachea  and  bronchi. 
There  is  a  recent  x-ray  burn  and  scar  6  cm.  long  above  the 
clavicle,  beneath  which  there  is  diffuse  purulent  inflammation  of 
subcutaneous  tissues.  One  cervical  node  shows  diffuse  casea- 
tion. The  oldest  most  altered  nodes  appear  in  the  right  mid- 
cervical  region  close  to  the  pharynx. 

Anatomical  Diagnosis:  Chronic  caseous  cervical  lymph- 
adenitis. Lymphomata  of  thoracic  and  abdominal  lymph  node, 
axillary  and  inguinal  nodes.  Hyperplasia  of  spleen.  Acute 
pneumonia. 

Liver:  Portal  canals  are  the  seat  of  miliary  and  diffuse 
lymphomatoses.  The  capillaries  contain  many  lymphocytes  as 
in  leukemia.    Extensive  pigmentation. 

Larynx :  At  the  base  of  the  laryngeal  sinus  is  a  deep  necrotic 
ulcer  of  rather  old  standing,  measuring  1.5  cm.  Mediastinal 
tumor  is  composed  of  diffuse  lymphomatosis  with  much  fibrous 
tissue. 

Kidney  is  seat  of  miliary  lymphomatosis.  The  bloodvessels 
are  packed  with  lymphocytes;    acute  degeneration. 


72  coley:  neoplasms  of  the  lymphatic  glands 

Lungs:    Necrotic  bronchopneumonia. 

The  clinical  history  of  this  case  together  with  the  autopsy 
findings  illustrates  how  difficult  it  is  to  distinguish  between 
lymphosarcoma  and  the  conditions  designated  as  pseudoleukemia 
and  leukemia.  Here  I  beheve  we  had  to  deal  with  a  primary 
lymphosarcoma  of  the  tonsil  which  later  gave  rise  to  secondary 
glandular  metastases,  resembling  the  lesions  found  in  leukemia 
and  pseudoleukemia. 

Case  XXXIX. — Lymphosarcoma  of  the  neck. 

J.  J.,  female,  aged  twenty-five  years.  In  November,  191 2, 
she  first  noticed  slight  disability  of  right  hand;  treated  at  Van- 
derbilt  Clinic  for  four  months.  On  February  17, 1913,  she  noticed 
a  small  nodule  on  the  right  side  of  the  neck  below  the  inferior 
maxilla.  This  grew  very  rapidly,  and  was  excised  at  Roosevelt 
Hospital  on  April  19,  1913.  The  specimen  was  examined  by  the 
pathological  department  of  the  hospital,  whose  report  dated 
April  8,  1913,  reads  as  follows: 

"Simple  lymphoma;  further  sections  show  numerous  large 
epitheloid  cells,  some  of  which  are  multinucleated,  also  more 
eosinophiles ;  the  struma  is  not  markedly  increased,  but  is 
definite.  This  tumor  has  many  of  the  characteristics  of  an  infec- 
tious granuloma  and  is  probably  due  to  the  early  changes  of 
Hodgkin's  disease.    Chronic  lymphadenitis." 

The  disease  recurred  in  June,  19 13,  and  was  accompanied 
by  much  pain.  A  second  operation  was  performed  at  St.  Luke's 
Hospital.  The  report  of  the  microscopic  examination  made 
at  this  time  (November  12,  1913)  reads  as  follows: 

"Diagnosis:  sarcoma  of  neck.  The  tumor  tissue  proper  is 
formed  by  small  round  cells  of  lymphoid  type,  arranged  loosely, 
which  stain  deeply.  There  is  a  delicate  fibrous  reticulum  in 
which  there  are  many  thin-walled  bloodvessels  and  numerous 
areas  of  adipose  tissue.  No  giant  or  multinuclear  cells  are  found. 
Where  the  cells  invade  the  surrounding  muscle,  they  lose  their 
alveolar  arrangement  and  lie  scattered  individually  in  the 
connective  tissue." 

Again  a  recurrence  took  place  and  on  September  23,  191 3,  the 


coley:  neoplasms  of  the  lymphatic  glands  73 

patient  was  admitted  to  the  General  Memorial  Hospital.  Physi- 
cal examination  at  this  time  showed  several  large  tumor  masses 
occupying  the  whole  right  cervical  region,  some  made  up  of  more 
or  less  discrete  glandular  tumors,  others  apparently  formed  by 
fusing  together  of  a  number  of  smaller  nodules.  A  mass  was 
also  felt  in  the  abdomen,  probably  a  retroperitoneal  gland. 
Axillary  and  inguinal  glands  were  slightly  involved;  no  enlarge- 
ment of  spleen  or  liver.  Wassermann  negative.  Blood  exami- 
nation showed  the  following:  Leukocytes,  14,500;  poly- 
nuclears,  88  per  cent.;  mononuclears,  10  per  cent.;  eosinophiles, 
2  per  cent.  There  were  several  pigmented  areas  and  warts 
over  the  chest  wall. 

The  patient  was  put  upon  radium  treatment  and  received 
seven  applications  between  October  11  and  November  20, 
varying  in  duration  from  sixteen  to  twenty  hours.  In  spite  of 
some  local  improvement,  her  general  condition  gradually  became 
worse,  later  associated  with  nausea  and  vomiting;  death  oc- 
curred on  December  14,  1913. 

This  case  is  interesting  from  the  different  pathological  report 
at  different  stages  of  the  disease,  as  also  from  the  comparatively 
short  duration  of  life. 

Case  XL. — Lymphosarcoma  of  the  tonsil  with  metastasis  in 
the  neck;  generalization  of  disease;  diphtheroid  bacillus  found  in 
glands. 

J.  McA.,  male,  aged  twenty-six  years.  Family  history:  no 
tuberculosis,  syphilis,  or  cancer.  Personal  history:  Always  in 
good  health  until  July,  1913,  when  he  noticed  some  difficulty 
in  swallowing,  and  found  that  the  right  tonsil  had  become  en- 
larged. A  small  lump  appeared  also  at  the  angle  of  the  jaw, 
right  side,  about  the  same  time.  Under  local  treatment,  the 
patient  believed  that  the  swelling  of  the  tonsil  completely 
disappeared.  Early  in  September,  1913,  it  again  became  en- 
larged and  grew  rather  rapidly  in  size;  the  gland  in  the  neck 
also  increased  in  size.  Tumor  of  the  tonsil  was  removed  in 
September,  and  the  following  month  a  local  recurrence  took 
place.    In  the  beginning  of  October,  1913,  a  small  gland  appeared 


74  coley:  neoplasms  of  the  lymphatic  glands 

on  the  left  side  of  the  neck.  On  October  21,  1913,  a  specimen 
was  removed  from  the  tonsil  and  examined  by  the  pathologist 
at  Bellevue  Hospital;  who  pronounced  it  lymphosarcoma. 

The  patient  was  admitted  to  my  service,  at  the  General  Mem- 
orial Hospital,  on  November  7,  19 13.  Physical  examination  at 
that  time  showed  a  large  tumor. of  the  right  tonsil  pushing  the 
uvula  to  the  left,  and  extending  up  behind  the  soft  palate, 
The  tumor  was  of  rather  firm  consistence.    On  the  right  side  of 


Fig.  32. — Case  XL.  Lymphosarcoma  of  tonsil  and  neck  (Dr.  Ewing 
and  also  Bellevue  Hospital  Laboratory).  Pure  culture  of  diphtheroid  bacillus 
obtained  from  gland  in  neck. 

the  neck  was  a  large  tumor,  measuring  six  and  a  quarter  inches 
by  four  inches  in  diameter,  apparently  made  up  of  several  large 
glands  more  or  less  closely  fused  together.  Tumor  markedly 
firm  in  consistence,  skin  normal  in  appearance.  On  the  left 
side  was  a  gland  about  the  size  of  an  English  walnut,  freely 
movable  beneath  the  angle  of  the  jaw.  Axillary  glands  palpable; 
inguinal  glands  enlarged;    no  enlargement  of  spleen  or  liver. 


coley:  neoplasms  of  the  lymphatic  glands  75 

The  patient  was  put  upon  the  mixed  toxins  of  erysipelas 
and  Bacillus  prodigiosus  on  November  8,1913,  and  from  that  time 
on  until  January  24,  he  received  thirty-seven  doses,  the  highest 
being  20  minims.  Soon  after  the  treatment  was  begun,  there  was 
marked  decrease  in  size  of  both  the  tonsillar  tumors  and  the 
tumors  in  the  neck.  The  improvement  was  only  temporary, 
however,  and  later  on  the  tonsillar  and  neck  tumors  began  to 
increase  in  size.  On  January  15,  1914,  under  ether  anesthesia 
a  large  tumor  of  the  right  side  was  removed  as  completely  as 
possible.  The  external  carotid  was  tied  and  very  extensive 
dissection  of  the  neck  was  made  by  my  associate,  Dr.  Downes. 
From  the  tumors  removed,  autogenous  vaccine  was  made  by 
Dr.  Weil,  and  from  February  10  to  February  30,  eight  doses 
of  vaccines  were  given.  On  February  7,  three  weeks  after  the 
operation,  both  sides  of  the  neck  were  almost  normal  in  appear- 
ance. There  was  still  a  large  mass  in  the  region  of  the  right 
tonsil.  February  23,  the  tonsillar  tumor  was  much  smaller, 
and  the  tumor  of  the  neck  showed  considerable  decrease  in  size, 
Soon  after,  however,  the  tumors  again  began  to  grow  rapidly, 
and  some  killed  cultures  of  the  diphtheroid  bacillus,  which  were 
found  when  the  tumors  were  removed  at  the  time  of  operation 
in  January,  were  prepared  by  Dr.  Torrey,  of  the  Cornell  Labora- 
tory, and  treatment  was  started.  The  diphtheroid  bacillus 
cultures  were  given  on  March  4,  13,  16,  20,  during  which  period 
there  was  considerable  diminution  in  the  size  of  the  tumors. 
This  improvement  also  proved  only  temporary,  and  in  the 
latter  part  of  March,  the  tumors  again  began  to  increase  rapidly 
in  size.  X-rays  were  then  given  for  a  number  of  weeks,  by  Dr. 
Holding,  with  marked  temporary  improvement.  About  four 
weeks  later  the  disease  started  to  progress  more  rapidly  than 
ever  before;  evidence  of  metastasis  developed,  and  the  patient 
became  much  weaker.    He  died  of  exhaustion  on  June  14,  19 14 

Autopsy  Report  (June  15,  19 14). 

Body:  Very  much  emaciated.  Large  subcutaneous  mass  in 
left  side  of  neck,  also  a  large  mass  in  region  of  right  ear.  Edema 
of  legs  especially  left.     Recent  adhesion  of  right  pleura.     Large 


76  coley:  neoplasms  oe  the  lymphatic  glands 

tumor  attached  to  right  side  of  spinal  column  in  pleural  cavity, 
eroding  bone.  Glandular  enlargement  in  upper  dorsal  region 
in  front  of  spinal  column.  Large  mass  present  in  lumbar  region 
in  front  of  spinal  column. 

Liver:   Enlarged,  normal  appearance,  no  metastases. 

Heart:  Pericardium  normal.  Size  of  heart  normal.  Valves 
normal.     Multiple  subpericardial  flat  metastases. 

Lungs:  Uniformly  congested.  No  metastases.  One  small 
bronchia]  node  invaded. 

Spleen:  Moderately  enlarged,  deep  red.  One  small  pea-sized 
metp^stasis. 

Kidneys:  Both  kidneys  extensively  invaded  by  bulky,  diffuse, 
circumscribed  tumor  mass.  In  one  the  main  tumor  mass  is 
extrarenal  and  extracapcular.  Invasion  is  from  lower  poles  of 
kidney.     Renal  cortex  thick,  markings  indistinct. 

Adrenals:    Negative. 

Pancreas:    Normal. 

Stomach:  Shows  twelve  extensive,  fiat,  ulcerating,  submucous 
infiltrations.  Ileum  shows  many  numerous  fiat  infiltrations, 
involving  chiefly  tips  of  valvulae.  Mesenteric  nodes  all  mod- 
erately enlarged. 

Bladder:    Normal. 

Prostate:    Normal. 

Mouth:  Left  side  of  base  of  tongue,  tonsil,  epiglottis,  and 
pharynx  is  seat  of  old  partly  cicatrized  ulcer,  which  connects 
with  several  large  cervical  lymph  nodes. 

Testes :    Palpate  normally. 

Microscopic:  Ulcer  of  pharynx,  tongue,  and  epiglottis  is 
backed  by  a  large-celled  lymphosarcoma,  but  the  ulcer  extends 
far  beyond  the  limits  of  sarcoma,  and  may  stand  as  a  probable 
portal  of  entry  of  an  infection. 

Kidney:  Diffuse  large-celled  lymphosarcoma  with  extensive 
degeneration  of  tubule  cells. 

Liver:  Shows  miliary  abscesses  about  the  central  or  hepatic 
veins.  The  intestinal  lesions  show  lymphosarcoma  in  mucous 
and  submucous  coats. 


coley:  neoplasms  of  the  lymphatic  glands  77 

Spleen:  Shows  slight  hypertrophy  of  Malpighian  bodies  with 
beginning  lymphosarcoma. 

Stomach:  Diffuse  lymphomatosis  of  the  mucosa  and  sub- 
mucosa  lymph  nodes.  Thoracic  lymph  nodes  show  diffuse 
lymphosarcomatosis  with  fecaj  necrosis. 

Lymph  Nodes:  Structure  varies.  Original  tumor  from  neck 
showed  large  clear  cells  of  endothelial  type.  Second  neck  tumor 
excised  after  toxins  and  ic-ray  showed  much  necrosis  and  foci 
of  large,  round,  atypical  cells  as  in  lymphosarcoma.  Internal 
nodes  at  autopsy  and  metastases  all  show  typical  large  or  medium- 
cell  lymphosarcoma.  As  the  process  became  more  active,  the 
type  of  cell  appears  to  have  changed. 

Case  XLI. — Lymphosarcoma  of  cervical  glands  resembling 
Hodgkin^s  Disease. 

G.  A.  L.,  male,  aged  thirty-one  years.  Family  history  nega- 
tive! Father  died  of  arteriosclerosis  and  interstitial  nephritis; 
mother  and  five  brothers  alive  and  well;  no  history  of  any 
malignant  growth  on  either  side  of  the  family.  From  1903  to 
1908,  the  patient  has  been  somewhat  subject  to  tonsillitis;  he 
noticed  that  the  submaxillary  and  cervical  glands  had  a  ten- 
dency to  become  swollen  and  painful  at  the  times  of  these  attacks 
but  the  swelling  always  subsided  afterward.  In  1906  a  scantling 
fell  from  a  distince  of  six  to  eight  feet,  one  end  striking  him 
upon  the  neck.  He  always  claimed  that  this  particular  spot 
became  a  hard  and  painful  lump  at  the  times  of  the  tonsillar 
infections  and  subsided  with  the  sore  throat.  In  October,  1908, 
following  an  attack  of  tonsillitis,  the  usual  disappearance  on 
recovery  did  not  take  place.  The  lump  continued  to  grow  and 
was  removed  by  his  brother.  Dr.  G.  E.  Leavitt,  of  Yerington, 
Nevada.  At  this  operation  several  small  glands,  in  addition  to 
the  larger  tumor,  which  was  about  the  size  of  an  English  walnut, 
were  rernoved.  Two  glands  were  examined  by  Dr.  William 
Ophiils,  of  San  Francisco,  who  reported: 

"Sections  of  both  glands  show  a  filling  of  lymph  spaces  with 
very  large  polygonal  cells  with  large  vesicular  nuclei  without 
intercellular  substance.     The  dividing  line  between  these  cells 


78  coley:  neoplasms  of  the  lymphatic  glands 

and  the  adjoining  tissue  is  quite  sharp  in  many  places,  in  other 
parts  layers  of  epithelial  cells  are  interposed  between  the  large 
cells  and  the  lymph  adenoid  tissue.  There  are  also  nodules  and 
irregular  areas  of  epithelioid  cells.  Some  of  these  areas  show 
central  caseation.  The  centre  of  some  of  the  nodules  is  formed 
by  partly  necrotic  tumor  tissue.  Diagnosis:  Lymphosarcoma 
of  the  cervical  glands  complicated  with  tuberculosis." 

Dr.  James  Ewing,  of  Cornell  University  Pathological  Depart- 
ment, disagreed  with  the  diagnosis  of  tuberculosis  and  reported 
endotheliomata. 

Early  in  November,  1908,  when  the  patient  came  under  my 
care,  there  were  several  recurrent  enlarged  glands  in  the  right 
cervical  region.  He  was  immediately  put  upon  the  mixed 
toxins.  At  the  end  of  six  weeks  the  tumors  had  entirely  dis- 
appeared and  the  patient  returned  home,  where  the  treatment  was 
continued  with  occasional  intervals  of  rest.  Following  his 
return  from  New  York  to  June  i,  1909,  his  health  was  good  and 
his  weight  remained  stationary.  Soon  after  the  evidence  of  a 
recurrence  became  apparent.  On  January  20,  1910,  the  glands 
in  the  right  inguinal  and  right  cervical  region  were  excised  by 
Dr.  Pickard,  of  Reno,  Nevada.  At  this  time  pressure  symptoms 
in  the  right  leg  had  developed  and  irregular  masses  appeared 
above  Poupart's  ligament  on  both  sides.  Dr.  Ophiils's  report 
on  the  glands  removed  on  January  20,  1910,  read: 

"Section  shows  the  same  structure  as  found  in  specimen  of 
October,  1908.  Much  new-formed  dense  fibrous  tissue  is  encap- 
sulated in  the  lymph  adenoid  tissue.  Largely  in  the  region  of 
the  lymph  spaces  the  rather  badly  defined  masses  of  very  large 
irregular  cells  with  vrey  large  vesicular  nuclei  without  inter- 
cellular substance.  There  are  large  necrotic  areas  in  the  centre 
of  some  groups  of  cells.  In  other  places  there  are  areas  sur- 
rounded by  epithelioid  cells.  Diagnosis:  malignant  lymphoma 
of  cervical  and  inguinal  lymph  glands." 

The  toxins  were  again  tried  with  little  or  110  effect;  he  con- 
tinued to  lose  weight  rapidly.  Later  vaccines  of  various  kinds 
were    tried    without    avail.      His    abdomen    gradually   became 


coley:  neoplasms  of  the  lymphatic  glands  79 

filled  with  tumors  which  extended  upward  from  Poupart's  liga- 
ment on  both  sides.  There  were  no  signs  of  mediastinal  involve- 
ment. Death  occurred  on  November  5,  1910,  just  two  years 
from  the  time  I  first  saw  the  patient. 

Case  XLII. — Sarcoma  of  the  neck.  Microscopic  examination. 
Clinical  diagnosis:    Hodgkin^s  disease. 

R.  P.,  male,  aged  twelve  years,  was  admitted  to  the  General 
Memorial  Hospital  on  June  11,  191 5  (referred  to  me  by  Dr. 
Howard  Lilienthal) .  The  patient's  father  died  at  the  age  of  thirty- 
nine  years  of  pleurisy  and  consumption.  No  history  of  cancer  in 
family.  The  patient  had  measles  at  the  age  of  six  years;  other- 
wise nothing  important  in  the  personal  history  until  nine  weeks 
ago,  when  he  noticed  a  small,  movable,  painless  lump  in  the 
left  axilla;  since  then  has  had  occasional  attacks  of  pain.  Very 
soon  after  the  lump  was  discovered,  he  began  to  have  irregular 
fever  which  has  continued  up  to  the  time  of  admission.  He 
also  had  a  slight  cough.  Operation  four  weeks  ago  at  the  Jewish 
Hospital  in  Brooklyn.  Microscopic  examination  of  the  specimen 
removed  showed  the  disease  to  be  spindle-  and  round-celled 
sarcoma.  Almost  immediately  after  the  operation  similar  glan- 
dular tumors  were  noticed  on  the  left  side  of  the  neck  and  a  few 
days  later  also  on  the  right  side.  These  increased  in  size  rapidly 
and  the  patient's  general  health  deteriorated. 

Physical  examination  at  the  time  of  admission  to  the  General 
Memorial  Hospital  showed  two  large,  nodular  tumors  on  each 
side  of  the  neck,  extending  from  the  mastoid  above  down  to 
the  middle  of  the  sternomastoid  muscle;  tumor  fairly  mov- 
able; moderately  firm  in  consistence;  skin  not  adherent.  The 
right  submaxillary  and  submental  glands  are  involved.  There 
is  no  enlargement  of  spleen  or  liver;  inguinal  glands  not  en- 
larged. June  30:  The  patient  has  had  irregular  temperature 
since  he  entered  the  hospital,  ranging  between  101°  to  104° 
during  the  first  two  weeks;  he  was  then  put  upon  x-ray  treat- 
ment and  the  temperature  has  now  returned  to  normal;  the 
tumors  of  the  neck  have  almost  entirely  disappeared  and  his 
general  condition  seems  improved. 


8o  coley:  neoplasms  of  the  lymphatic  glands 

Subsequent  History:  Almost  immediately  after  the  disap- 
pearance of  the  tumors  in  the  neck  the  patient  showed  evidence 
of  a  tumor  mass  in  the  epigastric  region,  which  increased  rapidly 
in  size.  This  at  first  yielded  to  the  :r-ray  treatment,  but  later 
the  rays  had  Httle  effect.  At  the  end  of  two  weeks  the  glands 
in  the  neck  which  had  disappeared  under  :r-ray  recurred  and 
grew  rapidly,  and  the  patient's  general  condition  grew  steadily 
worse.     He  has  been  confined  to  his  bed  since  July  i. 

Blood  examination  made  June  i6  shows:  White-blood  cells 
8500;  hemoglobin,  88  per  cent.;  polynuclears,  46  per  cent.; 
large  mononuclears,  27  per  cent.;  transitional s,  7  per  cent.; 
lymphocytes,  20  per  cent. 

The  high  temperature  which  was  present  at  the  time  of  the 
patient's  admission  to  the  hospital  rapidly  subsided  and  became 
normal  after  the  tumors  of  the  neck  had  disappeared  under  the 
x-ray  treatment.  However,  upon  the  reappearance  of  the  glands 
in  the  abdomen  the  patient  again  showed  an  irregular  tempera- 
ture. He  became  rapidly  worse  and  died  on  August  15,  191 5, 
four  months  after  he  first  noticed  the  enlarged  gland  in  the 
axilla. 

Case  XLIII. — Recurrent  round-celled  sarcoma  of  the  cervical 
glands  (injective  granuloma). 

C.  S.  H.,  male,  aged  thirty-five  years,  was  referred  to  me  by 
Dr.  H.  L.  Smith,  of  Nashua,  Me.,  in  October,  1912,  with  the 
following  history:  He  first  noticed  a  nodule  in  the  neck  on  the 
left  side  eight  years  ago.  This  grew  very  slowly  for  six  years, 
but  more  rapidly  thereafter.  The  first  operation,  which  was  a 
extensive  one,  was  done  in  July,  1910,  by  Dr.  Smith  and  con- 
sisted in  ligation  of  the  common  carotid  and  dissection  deeply 
into  and  behind  the  pharynx  up  to  the  base  of  the  skull.  A 
portion  of  the  parotid  gland  was  removed,  also  a  portion  of 
the  auricle.  The  operation  was  believed  to  be  incomplete  and 
recurrence  was  regarded  as  certain.  Dr.  Kingsford,  pathol- 
ogist of  the  Dartmouth  Medical  School,  made  the  following 
report : 


coley:  neoplasms  of  the  lymphatic  glands  8 1 

"Sections  show  a  very  marked  infiltration  of  all  the  tissues 
with  round  cells.  The  remains  of  the  parotid  gland  can  still  be 
made  out,  but  the  function  of  the  gland  must  have  been  de- 
stroyed. The  round  cells  have  also  invaded  the  connective 
tissue  and  muscle,  and  in  many  places  the  round  cells  are  col- 
lected into  clusters  resembling  lymph  nodes.  Diagnosis:  round- 
celled  sarcoma  of  very  slow  growth." 

The  growth  recurred  promptly  and  continued  to  increase  in 
size.  When  the  patient  was  referred  to  me  in  November,  191 2, 
there  was  a  large  mass  on  the  side  of  the  face. 

The  ear  was  forced  outward  by  the  growth,  which  was  mainly 
above  and  in  front  of  it.  On  the  inside  of  the  cheek,  opposite 
the  superior  molars,  there  was  a  considerable  outcropping  of 
what  was  presumably  the  disease,  although  it  might  have 
been  of  inflammatory  character  resulting  from  the  interference 
with  the  salivary  duct.  It  has  been  very  painful  and  an  infected 
area  appeared  at  the  most  prominent  part  of  the  growth,  which 
broke  down  and  discharged  a  moderate  amount  of  grayish, 
sloughing  material. 

The  patient  entered  the  General  Memorial  Hospital  on  Novem- 
ber 30,  1912,  and  left  on  January  27,  1913,  during  which  time 
he  received  fifteen  injections  of  the  mixed  toxins,  the  highest 
dose  being  7.5  minims,  which  caused  a  very  severe  reaction.  The 
tumor  showed  steady  diminution  in  size  under  the  treatment, 
which  was  continued  by  his  family  physician  after  his  return 
home.  The  improvement  continued  for  some  time;  then  no 
further  decrease  was  noticeable,  and  on  November  18,  1913,  the 
patient  returned  to  the  General  Memorial  Hospital.  The 
toxins  were  given  in  larger  doses  and  x-rsij  treatment  was 
added.  This  was  followed  by  rapid  improvement,  and  when  the 
patient  left  the  hospital,  January  27,  19 14,  there  was  no  appar- 
ent evidence  of  the  disease  remaining.  The  toxins  were  con- 
tinued by  the  family  physician,  but  in  March  the  patient  devel- 
oped acute  nephritis,  to  which  he  succumbed  on  April  2,  1914. 
Dr.  Smith  stated  that  there  was  no  sign  of  a  recurrence  at  the 
time  of  his  death. 


82  coley:  neoplasms  of  the  lymphatic  glands 

Dr.  Swing's  report  on  a  section  of  the  original  tumor  reads 
as  follows: 

April  2,  19 13.  "The  section  received  of  a  recurrent  tumor  of 
the  parotid,  shows  a  lymphoid  infiltration  of  the  salivary  glands. 
It  falls  in  that  group  which  I  term  Mikulicz's  disease. 

"The  process  began  as  an  infectious  granuloma  and  may 
run  into  lymphosarcoma.  In  this  case  it  is  difficult  to  say 
whether  the  infectious  or  neoplastic  elements  are  the  more 
prominent. 

"There  are  some  features  of  lymphosarcoma,  but  they  are  not 
prominent;  yet,  I  think  the  course  might  closely  resemble  a 
malignant  tumor. 

"There  is  some  hypertrophy  of  epithelial  alveoli  which  I 
do  not  regard  as  important." 

RARE   TYPES  OF  MALIGNANT   DISEASE  OF  THE   LYMPHATIC  GLANDS 

Case  XLIV. — Primary  neoplasm  of  the  lymphatic  glands  of  the 
axilla.  Histological  diagnosis:  perivascular  hemangioma  by  one 
pathologist;  mixed-celled  sarcoma  by  another:  melanoma  by  a  third. 

M.  E.,  female,  aged  thirty-six  years,  was  referred  to  me  by 
Dr.  A.  E.  Jaffin,  Jersey  City,  on  January  27,  1914,  with  the 
following  history:  January  19,  19 13,  she  first  noticed  a  peculiar 
sensation  in  the  right  axilla;  no  tumor  until  two  months  later, 
when  a  small  lump  appeared  in  the  axilla.  This  grew  rapidly 
and  was  removed  in  April,  1913,  one  month  after  it  was  first 
noticed  by  Dr.  Jaffin,  who  states  that  the  tumor  was  the  size  of 
a  small  hen's  egg,  soft  and  glandular  in  appearance,  very  juicy, 
with  quite  a  large  area  of  central  necrosis,  otherwise  appar- 
ently well  encapsulated.  The  report  of  the  microscopic  exami- 
nation made  by  Dr.  George  E.  McLaughlin,  of  Jersey  City, 
under  date  of  April  16,  19 13,  reads: 

"The  tissue  received  on  April  11,  1913,  which  consisted  of  a 
large  lymphatic  gland  the  size  of  an  egg  and  a  small  lymphatic 
gland,  have  been  sectioned,  stained,  and  examined  microscopic- 
ally,  and  I  would   report  as  follows: 


coley:  neoplasms  of  the  lymphatic  glands 


83 


"The  smaller  gland  showed  a  lymphadenitis,  while  the  large 
gland  was  made  up  of  a  fibrous  tissue  stroma  with  here  and  there 
some  coagulation  necrosis  and  large  numbers  of  dilated  blood- 
vessels. Surrounding  these  bloodvessels  were  cylindrical  bands 
of  endothelioid-like  cells  which  seemingly  had  their  origin  in 
the  adventitia  of  the  vessels.  The  nuclei  of  these  cells  took  the 
stain   well    and   were   large    and   somewhat   oval.      Diagnosis: 


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Fig.  33. — Case  XLIV.     Axillary   glands;    rapid   progress.      One   pathologist 
reported  sarcoma;  another  melanoma. 


perivascular  hemangiosarcoma.     This  growth  is  malignant  and 
capable  of  causing  metastasis." 

On  May  17, 1913,  one  month  later,  the  mixed  toxins  were  begun 
and  given  daily  or  every  other  day  for  two  months,  in  doses 
up  to  4  minims.  In  July  a  local  recurrence  was  noticed  and 
on  July  25  a  thorough  dissection  of  the  entire  axilla  was  done. 
The  specimen  was  submitted  to  Dr.  Mandlebaum,  of  the  Mt. 


84  coley:  neoplasms  or  the  lymphatic  glands 

Sinai  Hospital,  who  pronounced  the  disease  mixed-celled  sar- 
coma.   His  full  report,  dated  July  30,  1913,  reads  as  follows: 

"The  axillary  tumor  in  the  case  of  M.  E.  shows  mostly  large 
round  cells  of  a  sarcomatous  type  and  having  very  large  nuclei. 
In  a  few  situations  spindle  cells  are  also  seen.  Some  delicate 
connective-tissue  fibers  are  found  between  the  cells  in  places. 
Here  and  there  are  small  capillaries  which  seem  to  bear  some 
relation  to  the  tumor  growth,  though  this  is  hardly  sufficient  to 
warrant  the  diagnosis  of  a  hemangiosarcoma.  In  my  opinion 
the  tumor  is  a  mixed-celled  sarcoma,  with  a  predominence  of 
large  round  cells,  and  is  very  likely  primary  in  the  lymph  nodes 
of  the  axilla,  even  though  no  lymphoid  tissue  is  to  be  found  in 
the  sections. 

"The  dark  areas  in  the  specimen  represent  localized  areas  of 
necrosis." 

On  August  8,  1 9 13,  the  toxins  were  resumed  and  the  dose 
increased  to  5  minims. 

November  29,  a  small  recurrent  nodule  was  found  overlying 
the  axillary  vein. 

January  5,  19 14,  third  operation.  The  portion  of  the  axillary 
vein  involved  by  the  tumor  was  resected. 

Physical  examination,  January  27,  1914,  showed  apparently 
no  recurrence.  Massive  a;-ray  treatment  advised  in  conjunction 
with  the  mixed  toxins.  The  tumor,  however,  soon  recurred 
and  on  February  19,  1914,  a  fourth  operation  was  performed, 
which  was  an  incomplete  one  owing  to  the  extent  of  the  disease. 
The  toxins  and  x-rays  were  resumed  with  little  effect  in  checking 
the  rapid  progress  of  the  disease. 

Examination  of  the  tumor  removed  at  the  third  operation  was 
made  by  Dr.  James  Ewing,  who  pronounced  it  a  melanoma. 

Bearing  on  the  possibility  of  the  tumor  having  been  secondary 
to  a  primary  melanoma  elsewhere,  it  may  be  mentioned  that 
the  patient  stated  that  a  year  ago,  she  noticed  a  small  spot 
three  inches  above  the  wrist  on  the  inner  surface  of  the  right 
forearm;  this  was  reddish  in  color  but  later  became  dark.  It 
never  ulcerated  and  never  showed  any  elevation  of  surface,  nor 


coley:  neoplasms  of  the  lymphatic  glands 


85 


did  it  seem  to  have  the  appearance  of  a  melanoma.  I  excised  it 
and  microscopic  examination  showed  no  evidence  of  melanoma. 

The  patient  died  in  August,  1914,  at  which  time  the  growth 
had  reached  the  size  of  a  child's  head  and  began  to  break  down. 
There  was  enormous  edema  of  the  arm  and  forearm. 

Case  XLV. — Melanotic  sarcoma  of  submaxillary  and  cervical 
glands. 


Fig.  34. — Case  XLV.  Melanoma;  sarcoma  of  cervical  glands;  regarded 
as  tuberculosis  at  first;  two  operations.  Pathological  report  melanoma.  No 
primary  pigments. 

J.  M.  M.,  female,  aged  forty-three  years.  One  sister  died  of 
carcinoma  of  the  breast  in  July,  191 1,  after  having  undergone 
two  operations.  Mrs.  M.  took  care  of  her  the  entire  time. 
Shortly  after  her  death  she  noticed  an  enlargement  of  the  sub- 
maxillary lymph  gland.  This  was  never  very  painful  nor  did 
it  ever  show  evidence  of  inflammation  of  the  skin;  there  is  no 
history  of  a  wart  or  pigmented  mole  having  been  noticed  in  the 
vicinity  of  the  tumor.    The  patient  was  examined  by  Dr.  Irvin 


86  coley:  neoplasms  of  the  lymphatic  glands 

Abell,  of  Louisville,  Ky.,  in  October,  191 1,  who  found  a  smooth, 
movable  tumor,  the  size  of  a  guinea-hen's  egg  in  the  submaxil- 
lary region;  no  evidence  of  inflammation.  The  swelling  de- 
creased somewhat  under  local  applications  and  then  remained 
stationary.  Clinical  diagnosis:  Enlarged  lymph  gland  of  sub- 
maxillary group.  In  January,  191 2,  under  local  anesthesia,  the 
enlarged  gland  was  dissected  out  and  examined  by  Dr.  E.  S. 
Allen,  who  pronounced  the  trouble  chronic  adenitis,  non-tuber- 
culous. The  disease  recurred  a  few  months  later  and  a  second 
operation  was  performed  on  October  i,  191 2,  under  general 
anesthesia;  a  gland  the  size  of  an  acorn  was  removed;  it  was 
deeply  situated  and  rested  right  over  the  left  internal  jugular 
vein.  A  second  recurrence  followed  not  long  afterward  and  a 
third  operation  was  done  on  April  i,  1913.  A  mass  supposed 
to  be  an  enlarged  cervical  gland  was  removed  which,  on  explor- 
ation proved  to  be  a  blood  clot,  which  diagnosis  was  confirmed 
by  Dr.  Allen.  The  disease  recurred  locally,  and  a  fourth  opera- 
tion was  performed  on  September  30,  19 14,  an  incision  being 
made  through  the  former  one  on  the  left  side  of  the  neck  and 
through  the  sternomastoid  muscle.  The  tumor  involved  the 
internal  jugular  vein,  so  that  a  small  portion  of  the  latter  was 
dissected  in  taking  out  the  mass.  The  surrounding  structures 
were  indurated  and  clinically,  the  disease  had  the  appearance 
of  sarcoma.  Microscopic  examination  of  the  gland  made  by 
Dr.  Graves,  of  the  University  of  Louisville,  showed  it  to  be 
melanotic  sarcoma. 

The  disease  promptly  recurred  and  on  December  30,  19 14,  the 
patient  was  referred  to  me  by  Dr.  Abell,  for  the  toxin  treatment. 
Physical  examination  at  this  time  showed  the  patient  in  fairly 
good  health.  The  left  cervical  region  showed  several  scars. 
In  the  upper  portion  of  the  neck,  anterior  to  the  sternomastoid 
muscle  or  partly  involving  it,  is  a  tumor  the  size  of  a  hickory 
nut,  movable  upon  the  deep  structures,  firm  in  consistence; 
skin  slightly  adherent.  Just  above  the  clavicle  are  some  in- 
durated areas.  No  evidence  of  tumors  elsewhere.  The  patient 
was  put  upon  the  mixed  toxins  of  erysipelas  and  Bacillus  pro- 


coley:  neoplasms  of  the  lymphatic  glands  87 

digiosus  with  the  result  that  at  the  end  of  two  weeks  there  was 
considerable  decrease  in  size  and  marked  increase  in  mobility. 
Under  ether  anesthesia  I  removed  the  masses  as  thoroughly  as 
possible,  although  the  operation  was  by  no  means  complete. 
The  wound  healed  by  primary  union  and  the  toxins  were  im- 
mediately resumed  and  have  been  kept  up  two  to  three  times 
a  week  ever  since  by  her  husband  who  is  a  physician  in  Louisville. 
Microscopic  examination  made  by  Dr.  James  Ewing,  whose 
report,  dated  December  29,  1914,  showed  the  disease  "mela- 
noma, malignant." 

The  patient  remains  free  from  recurrence  at  the  present 
time,  August  15,  191 5,  which  is  a  much  longer  period  than  she 
had  been  free  from  recurrence  before.  Of  course,  it  is  too  early 
to  speak  of  a  definite  result. 

This  case  together  with  the  case  just  reported  suggest  that 
melanotic  sarcomas  or  melanomas  may  originate  in  the  lymphatic 
glands,  contrary  to  the  opinion  generally  held. 

Contrary  to  accepted  views,  the  two  following  cases  of  car- 
cinoma apparently  originated  in  the  axillary  glands. 

Case  XLVL — Primary  carcinoma  of  the  axillary  glands. 

Mrs.  L.,  aged  thirty-eight  years;  married;  was  formerly  a 
nurse  at  the  Hospital  for  Ruptured  and  Crippled.  The  patient 
was  first  seen  by  me,  in  consultation  with  Dr.  E.  L.  Barnett, 
in  October,  1913.  Family  history  negative.  Personal  history: 
About  nine  months  previously  the  patient  first  noticed  a  small 
movable  lump  in  the  outer  aspect  of  the  right  axilla,  about  the 
size  of  a  marble.  This  slowly  increased  in  size,  but  there  was  no 
pain  at  any  time.  No  lump  could  be  noticed  on  the  breast  nor 
could  any  tumor,  or  change  in  consistence,  be  made  out  upon 
careful  examination  of  the  breast.  On  October  10,  1913,  under 
ether  anesthesia,  I  operated  upon  her,  at  the  Hospital  for  Rup- 
tured and  Crippled,  and  found  a  freely  movable  tumor  the  size 
of  a  English  walnut  in  the  right  axilla.  No  other  glands  could 
be  felt  higher  up,  nor  could  any  tumor  or  induration  of  any  sort 
be  detected  in  the  breast,  under  anesthesia.  A  clinical  diagnosis 
of  malignancy  was  made,  but  in  view  of  the  fact  that  no  tumor 


88  coley:  neoplasms  or  the  lymphatic  glands 

could  be  felt  in  the  breast,  and  the  disease  was  apparently  pri- 
mary in  the  axillary  glands,  it  was  thought  to  be  either  a  sarcoma 
or  Hodgkin's  disease. 

A  specimen  was  sent  to  Dr.  Ewing  for  examination,  whose 
report,  dated  October  i8,  1913,  reads:  "Malighajit  adenocar- 
cinoma of  lymph  node." 

Dr.  Ewing  believed  it  to  be  secondary  to  some  primary  tumor 
elsewhere,  probably  in  the  breast.  The  patient  absolutely 
refused  to  undergo  a  further  operation.  She  was  pregnant 
at  the  time  of  the  first  operation,  and  a  few  months  thereafter 
gave  birth  to  a  healthy  child.  Since  that  time  she  has  been 
kept  under  careful  observation  by  Dr.  Barnett,  who  states  that 
at  the  time  of  his  last  examination,  a  few  months  ago,  there  could 
be  found  no  evidence  of  any  return  of  the  growth,  nor  has  any 
signs  of  a  tumor  in  the  breast  developed. 

In  connection  with  the  preceding  case  I  would  like  to  add  the 
following : 

Case  XL VII. — Carcinoma  of  the  axillary  glands,  apparently 
primary. 

Mrs.  C.  C.  W.,  was  referred  to  me  by  Dr.  R.  R.  Sinclair,  of 
Westfield,  N.  J.,  on  September  11,  1912.  Family  history  good. 
Persona]  history:  First  noticed  a  small,  hard,  gland  in  the 
right  axilla  one  year  prior  to  my  first  observation.  This  gland 
slowly  increased  in  size,  and  later  became  attached  to  the  skin. 
No  history  of  malignant  tumor  in  any  other  part  of  the  body. 

Physical  examination  showed  a  small  gland,  the  size  of  a 
hazel-nut  in  the  right  axilla,  freely  movable,  hard  in  consistence, 
clinically  a  typical  carcinoma.  The  skin  was  not  adherent.  No 
other  glands  could  be  felt  in  the  axilla,  or  above  or  below  the 
clavicle.  Careful  observation  failed  to  reveal  any  tumor  in  the 
breast  or  any  change  in  its  consistence.  Under  ether  anesthesia 
I  removed  the  tumor,  which  was  examined  by  Dr.  Ewing,  and 
pronounced  a  typical  carcinoma. 

The  patient  was  then  put  upon  the  mixed  toxins  of  erysipelas 
and  Bacillus  prodigiosus  in  the  hope  of  retarding  or  preventing 
a  recurrence.     She  remained  well  for  one  year,  when  a  small 


coley:  neoplasms  of  the  lymphatic  glands  89 

local  recurrence  in  the  axilla  developed,  which  was  again  re- 
moved by  operation,  and  the  toxins  continued  by  the  family 
physician.  She  remained  well  for  almost  another  year  before 
a  second  local  recurrence  developed,  which  was  again  removed, 
and  the  toxins  resumed  in  small  doses. 

Examination,  December  22,  1914,  showed  that  her  general 
health  had  remained  normal.  Shortly  after  this  she  developed 
a  small  swelling  above  the  right  clavicle,  which  has  slowly 
increased  in  size  ever  since.  During  the  last  six  months  she 
has  had  some  swelling  of  the  arm,  and  there  is  evidence  of  a 
recurrence  in  the  axilla.  Up  to  the  present  time  there  has 
never  been  any  tumor  whatever  in  the  breast  itself.  Her  con- 
dition is  gradually  getting  worse,  and  the  diseases,  which  has 
been  kept  in  fairly  good  control  with  the  toxins  during  the  last 
three  years,  is  steadily  progressing.    (Patient  died  January,  19 16.) 

Case  XL VIII. — Lymphosarcoma  of  neck,  clinical  diagnosis 
"probably  endothelioma''  microscopical. 

G.  J.  C,  male,  aged  forty-four  years;  referred  to  my  service 
at  the  General  Memorial  Hospital  by  Dr.  Spencer,  of  Brooklyn, 
on  November  30,  191 2.  Wassermann  was  negative.  In  June, 
191 2,  he  first  noticed  a  lump  behind  the  sternomastoid  muscle 
on  the  right  side  of  the  neck.  He  gave  a  history  of  having 
had  severe  stiffness  on  the  right  side  of  the  neck,  one  year  before, 
accompanied  by  some  swelling  which  lasted  six  weeks,  during 
which  time  he  could  neither  eat  nor  sleep  and  lost  twenty-five 
pounds  in  weight.  The  swelling  entirely  disappeared  under  local 
treatment  and  he  became  as  well  as  ever.  In  June,  191 2,  the 
swelling  came  back  apparently  at  the  same  place,  but  more 
circumscribed,  without  any  stiffness  or  pain,  and  without  loss 
of  weight.  When  I  first  saw  the  patient,  in  November,  191 2, 
physical  examination  showed  a  tumor  the  size  of  a  closed  fist, 
occupying  the  entire  region  of  the  right  side  of  the  neck,  from 
the  mastoid  to  the  clavicle  and  from  the  vertebral  line  behind 
to  the  angle  of  the  jaw  in  front,  firmly  fixed,  skin  not  adherent. 

There  were  no  enlarged  glands  on  either  side  of  the  neck; 
no   axillary  or  inguinal  glands;  no   enlargement  of  spleen   or 


90  coley:  neoplasms  or  the  lymphatic  glands 

liver.  The  patient  had  had  ii;-ray  and  iodide  of  potassium  treat- 
ment without  improvement  before  going  to  the  Hospital.  I 
made  the  clinical  diagnosis  of  sarcoma.  The  mixed  toxins  were 
given  first  systemically,  later  locally  into  the  tumor.  At  first 
there  was  some  diminution  in  the  size  of  the  growth  and  in- 
creased mobility.  A  portion  was  removed  for  microscopic  exam- 
ination and  submitted  to  Dr.  James  Ewing,  who  reported: 

"The  tissue  is  composed  of  diffuse  cohesive  masses  of  large 
polygonal,  round,  and  fusiform  cells  with  hyperchromatic  nuclei; 
many  mytoses,  one  hydropic  cell  between.  There  are  no  definite 
epithelial  characters.  There  is  little  connective- tissue ;  the 
cells  are  often  arranged  about  frozen  bloodvessels.  There  are 
polynuclear  giant  cells.  Diagnosis:  primary  tumor  of  lymph 
nodes,  probably  endothelioma." 

The  tumor  finally  began  to  increase  in  size  rapidly  and  the 
toxin  treatment  was  abandoned  after  about  two  months,  when 
the  patient  returned  to  his  home.     Later  history  unknown. 

Case  XLIX. — Hodgkin^s  disease  or  carcinoma  of  cervical  glands. 

H.  Y.  C,  male,  Chinese,  aged  twenty-four  years;  two  sisters 
suffering  from  gland  trouble;  both  living.  The  patient  first 
noticed  slight  pain  in  the  neck  in  the  latter  part  of  the  summer  of 
1910.  Soon  after  a  swelhng  of  the  neck  was  seen  to  appear  almost 
simultaneously  on  both  sides;  this  gradually  increased  in  size; 
in  March,  191 1,  he  noticed  that  the  tonsils  were  much  hyper- 
trophied;  they  were  promptly  removed  at  the  University  of 
Michigan  Hospital.  Microscopic  examination  showed  no  ^ign 
of  mahgnancy.  A  month  later  a  portion  of  the  tumpr  on  the 
left  side  of  the  neck  was  removed  and  pronounced  Hodgkin's 
disease  by  Dr.  C.  B.  Nancrede.  In  the  early  part  of  June,  191 1, 
another  portion  of  the  neck  tumor  was  removed  at  the  Massa- 
chusetts General  Holpital,  and  pronounced  small-celled,  lymph- 
adenoma  of  Hodgkin's  type,  by  Dr.  H.  F.  Hartwell,  of  Boston. 

Physical  examination  at  the  time  the  patient  was  first  seen 
by  me,  July  7,  191 1,  showed  the  left  side  of  the  neck  occupied 
by  a  tumor  extending  from  the  mastoid  process  to  two  inches 
above  the  clavicle  and  from  the  angle  of  the  jaw  backward 


coley:  neoplasms  of  the  lymphatic  glands  91 

nearly  to  the  vertebral  line;  there  is  a  recent  curved  cicatrix 
four  inches  long,  over  the  upper  part  of  the  tumor.  The  skin  is 
markedly  reddened  and  somewhat  adherent  to  the  tumor  which 
is  extremely  hard  in  consistence  and  firmly  fixed  to  the  deep 
structures;  apparently  all  the  tissues  are  infiltrated  from  the 
skin  to  the  spinal  column.  A  similar  tumor  occupies  the  right 
side,  but  the  same  is  not  quite  as  large  and  the  skin  is  less  red- 
dened. There  are  no  enlarged  glands  in  axillae  or  groins;  no 
enlargement  of  spleen  or  liver.  Patient  has  lost  very  little  in 
weight.  I  made  the  clinical  diagnosis  of  lymphosarcoma.  The 
toxins  were  tried  for  two  or  three  weeks  without  effect.  He 
grew  worse  rapidly  and  died  a  few  months  later. 

The  clinical  features  in  this  case  were  entirely  different  from 
those  usually  found  in  Hodgkin's  disease,  and  the  microscopic 
examination  of  the  recurrent  tumor  made  at  the  University 
of  Michigan  laboratory  pointed  strongly  to  a  true  neoplasm, 
probably  of  the  carcinomatous  type. 

The  following  case  is  of  interest  from  the  fact  that  the  micro- 
scopic examination  by  one  pathologist  was  sarcoma,  by  another, 
tuberculosis.  The  subsequent  history  proved  the  disease  to  be 
malignant. 

Case  L. — Lymphosarcoma  of  the  inguinal  glands. 

W.  C.  D.,  male,  aged  twenty-four  years.  Family  history: 
No  specific  or  tuberculous  disease;  Wassermann  negative. 
The  patient  was  referred  to  me  by  Dr.  Vail,  of  Belleville,  N.  J., 
on  October  16,  191 2,  with  the  following  history:  Always  in 
good  general  health  until  three  years  before,  when  he  first 
noticed  a  small,  movable  gland,  about  the  size  of  a  hazel-nut 
in  the  right  groin.  This  increased  so  slowly  in  size,  that  he 
did  not  call  a  doctor's  attention  to  it  until  the  beginning  of 
October,  191 1,  just  previous  to  which  time  it  has  begun  to 
grow  more  rapidly. 

Physical  examination  on  October  16,  191 2,  showed  the  right 
inguinal  and  iliac  regions  occupied  by  a  tumor  the  size  of  two 
fists,  apparently  made  up  by  a  large  number  of  enlarged  glands, 
more  or  less  fused  together,  with  semifiuctuation  in  the  most 


92  coley:  neoplasms  of  the  lymphatic  glands 

protuberant  portion.  The  skin  is  slightly  reddened  and  adherent 
in  places.  The  tumor  was  fairly  movable  below  but  firmly  fixed 
in  the  upper  part;  there  was  very  slight  enlargement  of  the  glands 
on  the  side,  none  in  the  axilla  or  neck;  no  enlargement  of  spleen 
or  liver.  A  portion  of  the  tumor  the  size  of  a  goose  egg  was 
removed  under  ether  and  microscopic  examination  was  made  by 
Dr.  Ewing,  who  pronounced  lymphosarcoma.  Dr.  W.  C.  Clark, 
who  examined  another  specimen,  pronounced  it  tuberculosis. 
The  patient  was  immediately  put  upon  the  mixed  toxins  and  at 
the  end  of  six  weeks  the  tumor  had  diminished  to  less  than 
one-third  its  original  size.  In  spite  of  continued  treatment  little 
further  improvement  was  noticed  and  soon  the  tumor  began  to 
increase  rapidly  in  size.  The  patient  was  then  given  injections 
of  colloid  of  copper  solution  in  large  doses,  for  a  number  of 
weeks  without  any  appreciable  effect.  He  lost  strength  and 
weight  more  rapidly  than  before  and  died  on  January  13,  1913. 
The  tumor  proved  to  be  lymphosarcona. 

Case  LI. — Tumor  of  carotid  gland;  microscopic  diagnosis; 
sarcoma  of  glands  of  neck,  left  tonsil  the  clinical  diagnosis. 

E.  E.,  aged  forty-five  years;  mother  died  of  cancer  of  brain. 
Previous  history  negative.  First  noticed  a  swelling  beneath 
the  left  sternomastoid  muscle  near  its  upper  attachment  in  the 
fallof  1903;  it  caused  no  pain,  but  some  difficulty  in  breathing. 
The  patient  was  admitted  to  the  General  Memorial  Hospital 
on  January  21,  1904.  Physical  examination  at  this  time  showed 
a  mass  in  the  left  side  of  the  neck,  just  beneath  the  sternomastoid 
muscle,  the  size  of  an  egg,  firm,  but  not  tender.  Examination 
of  the  throat  showed  a  swelling  on  the  left  side  of  the  pharynx 
involving  the  tonsil  and  extending  nearly  to  the  right  pharyngeal 
wall.  The  tumor  was  firm  in  consistence  but  not  at  all  tender. 
Operation,  assisted  by  Dr.  Downes,  was  performed  on  January 
25,  1904,  and  consisted  in  tracheotomy,  ligature  of  the  left 
external  carotid,  removal  of  the  left  submaxillary  gland.  Al- 
though the  lower  jaw  was  sawed  through  with  a  Gigli  wire  saw, 
it  was  found  impossible  to  remove  the  entire  tumor.  Micro- 
scopic  examination   made   by  Dr.  George   Biggs,  showed   the 


coley:  neoplasms  of  the  lymphatic  glands 


93 


specimen  to  be  a  "tumor  of  the  carotid  gland."    Later  history 
unknown. 


Fig.  35. — Case  LI.     Tumor  of  carotid  body  (tonsilinvolved). 


The  following  case  shows  the  probable  influence  of  trauma 
as  a  causative  factor  in  the  development  of  a  neoplasm  of  the 
lymphatic  glands: 

Case  LII. — Sarcoma  of  inguinal  glands. 

G.  S.,  aged  five  and  one-half  years.  Always  well  until  May, 
1899,  when  he  fell,  injuring  his  right  groin.  A  few  days  later 
a  soft  and  rapidly  growing  tumor  developed  at  the  site  of  the  in- 
jury. Its  rapid  development  and  semifluctuating  character  led 
Dr.  William  T.  Bull  to  believe  it  was  an  abscess.  Incision  showed 
only  blood  and  -a  very  vascular  tumor.  Microscopic  examination 
proved  it  to  be  a  small  round-celled  sarcoma.  The  iliac  glands 
became  quickly  involved.  The  mixed  toxins  were  tried  for  one 
month  and  while  at  first  the  tumor  became  much  more  movable 
and  perceptibly  smaller,  after  two  or  three  weeks  it  began  to 


94  coley:  neoplasms  of  the  lymphatic  glands 

increase  in  size  again  and  its  growth  could  no  longer  be  con- 
trolled. The  patient  died  in  September,  1899,  four  months  from 
the  time  of  the  injury. 

Case  LIII. — Lymphosarcoma  of  the  tonsil  with  secondary 
involvement  of  neck. 

Mr.  S.,  aged  fifty-five  years.  Wife  died  of  carcinoma  of  breast 
in  November,  1908.  In  the  early  part  of  November,  1909, 
while  traveling,  he  first  noticed  trouble  in  his  throat.  He  con- 
sulted Dr.  Landsman,  of  New  York,  who  found  what  seemed  to 
be  a  severe  tonsillitis  or  quinsy  and  treated  him  accordingly. 
His  temperature  ranged  from  102°  to  103°.  Inasmuch  as  after 
a  week's  treatment  his  temper ture  remained  high  and  his  general 
condition  unimproved,  he  consulted  Dr.  Clarence  C.  Rice, 
of  New  York,  who  suspected  malignant  trouble,  and:  I  was 
called  in  consultation.  Physical  examination  on  November  26, 
1909,  showed  the  patient  rather  thin,  with  sallow  complexion 
and  a  temperature  of  102°  to  103°,  pulse  120.  Examination  of 
the  throat  showed  the  left  tonsil  markedly  swollen,  being  of 
the  size  of  a  small  hen's  egg,  ulcerated  in  the  centre  over  an 
area  of  three-quarters  of  an  inch  in  diameter.  The  tonsil  was 
covered  with  a  foul,  grayish  exudate  in  the  central  portion.  The 
right  tonsil  was  also  somewhat  enlarged,  but  not  ulcerated.  I 
made  the  clinical  diagnosis  of  malignant  tumor  of  the  left  tonsil, 
whether  sarcoma  or  carcinoma  I  was  unable  to  say,  its  general 
appearance  and  consistence  was  more  that  of  carcinoma,  but 
its  size  and  rapid  growth  were  in  favor  of  the  diagnosis  of  sar- 
coma. The  left  cervical  glands  had  become  markedly  swollen, 
from  the  mastoid  to  the  clavicle,  some  of  the  tumors  being  the 
size  of  an  English  walnut.  •  The  glands  on  the  right  side  of 
the  neck  are  also  swollen,  especially  in  the  upper  portion. 

The  tonsillar  tumor  was  removed  and  the  specimen  submitted 
to  Dr.  James  Ewing,  professor  of  pathology  at  Cornell  Uni- 
versity, who  stated  that  the  tonsil  was  undoubtedly  malignant 
but  whether  it  was  carcinoma  or  sarcoma,  he  could  not  be  sure. 
He  desired  another  specimen  ,  and,  on  November  29,  under 
cocaine  anesthesia,  I  removed  a  small  gland  from  the  left  cervical 


coley:  neoplasms  of  the  lymphatic  glands  95 

region,  just  above  the  angle  of  the  jaw,  about  the  size  of  a 
hazel  nut;  it  was  soft  in  consistence  and  typically  malignant 
in  appearance.  Dr.  Swing's  report  on  the  tumor  was  as 
follows: 

"The  lymph  nodes  contain  lymphosarcoma.  The  structure 
indicates  a  high  degree  of  malignancy." 

After  a  more  careful  examination  of  the  specimen.  Dr.  Ewing 
stated  that  he  was  in  doubt  whether  it  was  lymphosarcoma  or 
Hodgkin's  disease.  The  tumors  of  both  tonsils  continued  to 
increase  rapidly  in  size  until  they  nearly  met,  making  swallowing 
extremely  difiticult.  The  ulcerated  area  in  the  left  tonsil  spread 
and  soon  the  right  tonsil  also  began  to  ulcerate.  Apparently 
the  right  side  had  become  infected  from  the  other  side  by  con- 
tiguity. 

On  December  2,  six  days  after  my  first  observation,  and 
three  weeks  from  the  first  signs  of  the  trouble,  his  temperature 
still  ranged  between  102°  to  103°.  His  local  and  general  con- 
dition rapidly  became  worse.  At  this  time  (December  2)  he 
received  the  first  injection  of  the  mixed  toxins  in  the  pectoral 
region,  one-fourth  minim  being  given.  This  was  followed  by 
a  severe  chill,  rigor  and  a  temperature  of  105°.  His  general 
condition  was  so  bad  that  it  was  thought  unwise  to  continue 
the  treatment  and  he  died  on  December  5,  the  entire  duration 
of  life  from  the  time  of  the  first  symptom  to  death  in  this  case 
was  three  weeks  and  two  days. 

Case  LIV. — Lymphatic  leukemia. 

N.  B.,  male,  aged  sixty-five  years,  was  admitted  to  my  service 
at  the  General  Memorial  Hospital  on  June  2,  19 13.  Family 
history  good.  Personal  history:  In  November,  191 2,  he  cut  his 
finger;  the  wound  did  not  heal  well  and  what  he  called  a  "dry 
sore"  remained  for  a  number  of  weeks.  This  was  followed  two 
months  later  by  an  eruption  upon  hands  and  face  and  neck. 
Ten  weeks  ago  he  first  noticed  fairly  good-sized  lumps  on  both 
sides  of  the  neck  which  came  on  very  suddenly  and  grew  rapidly; 
he  lost  fourteen  pounds  in  weight.  The  eruption  is  still  present 
over  face  and  body. 


96  coley:  neoplasms  of  the  lymphatic  glands 

Physical  examination  on  admission  showed  large  masses  on 
both  sides  of  the  neck,  freely  movable,  more  or  less  discrete, 
clinically  typically  characteristic  of  Hodgkin's  disease;  spleen 
markedly  enlarged,  liver  only  slightly. 

Blood  examination  June  2,  showed  white  blood  cells  200,000. 
The  patient  was  treated  with  the  ic-ray  and  later  also  with  vac- 
cine by  Dr.  Weil.  There  was  marked  decrease  in  the  number  of 
white  cells.  June  22:  White  blood  cells,  91,600;  hemoglobin,  81 
per  cent.  June  25:  White  blood  cells,  70,000;  hemoglobin,  69 
per  cent.     July  15:  White  blood  cells,  112,000. 

There  was  very  marked  diminution  in  the  size  of  the  glands 
under  the  treatment.  General  condition  remained  about  the 
same.    Later  history  not  known. 

Case  LV. — Case  of  pseudoleukemia  later  changing  into  leukemia. 

Mrs.  E.,  aged  forty-nine  years,  married,  referred  to  me  by 
Dr.  E.  M.  Foote,  was  admitted  to  the  General  Memorial  Hsopi- 
tal  on  March  2,  1915.  Family  history  good.  Personal  history: 
Ten  years  ago,  amputation  of  breast  for  carcinoma;  no  recur- 
rence; glycosuria  for  a  number  of  years;  disappeared  recently. 
Four  years  ago  first  noticed  a  swelling  in  the  submaxillary 
glands  on  the  left  side.  A  little  later  appearance  of  similar  glands 
on  the  other  side  of  the  neck,  shortly  followed  by  enlargement  of 
the  axillary  glands;  later  the  inguinal  glands  also  became 
involved.  The  patient  was  treated  at  various  hospitals  and  a 
number  of  glands  were  removed  at  different  times  for  diagnostic 
purposes.  The  family  physician  stated  that  ic-ray  and  benzol 
treatment  had  been  tried,  without  apparent  effect,  and  that  in 
May,  19 14,  her  blood  count  showed  38,000  white  cells  and  90 
per  cent,  of  lymphocytes. 

She  was  referred  to  me  by  Dr.  Foote  as  a  case  of  Hodgkin's 
disease.  Physical  examination  at  the  time  of  her  admission  to 
the  General  Memorial  Hospital  showed  enormously  enlarged 
glands  in  both  cervical  and  axillary  regions;  moderately  enlarged 
inguinal  glands;  spleen  and  liver  not  palpable;  some  resistance 
in  the  region  of  the  abdomen,  pointing  to  an  involvement  of  the 
mesenteric  glands,  but  on  account  of  her  stoutness,  these  could 


coley:  neoplasms  of  the  lymphatic  glands  97 

not  be  clearly  made  out.     Blood  examination  (March  3,  191 5) 
showed : 

White  cells,  164,000;  hemoglobin  68  per  cent.;  polynuclears, 
7  per  cent.;  eosinophiles,  i  per  cent.;  large  mononuclears,  9 
per  cent.;  lymphocytes,  83  per  cent. 

The  patient  was  put  upon  ic-ray  treatment.  Two  days  after 
the  first  application  the  blood  count  was  as  follows: 

White  cells,  107,000;  lymphocytes,  95  per  cent.;  large  mono- 
nuclears, 2  per  cent.;  polynuclears,  3  per  cent.  Many  degenerated 
white  blood  cells.     Red  cells  normal. 

On  March  16,  after  four  x-ray  treatments,  the  blood  examina- 
tion showed: 

White  cells,  80,000;  red  cells,  3,916,000;  hemoglobin,  60  per 
cent.;  lymphocytes,  86.6  per  cent.;  large  mononuclears,  10.7 
per  cent.;  pol3mLUclears,  2.7  per  cent. 

The  patient  was  discharged  from  the  hospital  on  March  23, 
1915.  The  last  blood  count,  March  20,  showed  white  cells  87,000. 
She  received  six  x-ray  treatments  during  her  stay  at  the  hospital 
and  has  continued  to  receive  treatment  in  the  out-patient 
department  since.  Examination  at  the  present  time,  August 
21,  shows  a  marked  decrease  in  the  size  of  all  glandular  tumors, 
but  her  general  condition  is  rapidly  deteriorating,  as  shown  by 
loss  of  weight  and  strength. 

Case  LVI. — Lymphosarcoma  or  melanoma,  apparently  primary 
in  the  axillary  glands. 

R.  B.  W.,  aged  twenty-four  years,  male;  graduate  of  medicine; 
had  been  in  good  health  until  the  last  of  November,  1914, 
when  he  had  an  attack  of  influenza;  a  week  later  he  notice 
enlargement  in  the  right  axillary  glands;  two  days  thereafter 
a  small  swelling  appeared  in  the  posterior  cervical  region  over 
the  lower  cervical  vertebra  at  the  base  of  the  neck;  all  tumors 
increased  rapidly  in  size.  He  entered  the  Toronto  General 
Hospital  on  December  2,  1914,  at  which  time  his  temperature 
was  100°.  The  first  two  weeks  it  ranged  between  96.5  to  99°, 
most  of  the  time  slightly  below  subnormal.  Blood  examina- 
tion showed:   Whites,  8000;  reds,  6,400,000;  hemoglobin,  85  per 


98  coley:  neoplasms  of  the  lymphatic  glands 

cent.;  differential  examination  showed  nothing  abnormal;  Was- 
sermann  negative.  The  patient  had  a  great  deal  of  pain  from 
the  beginning,  which  increased  with  the  progress  of  the  disease; 
the  pain  was  neuralgic  in  character  and  chiefly  confined  to  the 
chest  and  right  leg.  He  lost  rapidly  in  weight  and  strength 
and  on  January  9,  191 5,  when  the  patient's  father  consulted  me 
as  to  the  advisability  of  trying  the  toxins,  or  a  little  over  five 


Fig.  36. — Case  LVI.  Round-celled  sarcoma;  one  diagnosis.  Melanoma 
sarcoma.  Apparently  primary  in  lymphatic  glands  of  axilla;  death  in  three 
months.      (Ewing.) 

weeks  from  the  beginning  of  the  disease,  he  had  lost  eighteen 
pounds  in  weight.  He  died  January  10.  The  accompanying 
charts  show  the  origin  and  distribution  of  the  glandular  enlarge- 
ment. The  pathological  report  of  the  Toronto  General  Hospital 
read  "round-celled  sarcoma."  Some  of  the  slides  were  sent  to 
me  and  I  had  them  examined  by  Dr.  James  Ewing,  of  Cornell 
Medical  School  laboratory,  whose  report,  dated  April  21,  191 5, 
is  as  follows: 


coley:  neoplasms  of  the  lymphatic  glands 


99 


"The  materia]  received  consists  of  stained  sections  of  tumor 
tissue.  The  tissue  is  composed  of  compact  masses  of  large 
polyhedral  cells  arranged  in  ill-defmed  groups  separated  by  a 
little  stroma.  The  cells  are  poorly  fixed  and  very  hydropic, 
so  that  the  outlines  are  not  always  clear.  The  nuclei  are  large 
vesicular  and  hyperchromatic  with  prominent  nuclei;  miototic 
figures  are  very  numerous.  In  many  cells  there  is  an  abundance 
of  yellow  pigment  granules  and  some  cells  are  completely  filled 


Fig.  37. — Case  LVI.  Small  round- 
celled  sarcoma  of  axillary  glands,  with 
very  rapid  generalization. 


Fig.  38. — Case  LVI.  Small  round- 
celled  sarcoma  of  axillary  glands, 
with  very  rapid  generalization. 
Death  in  three  months. 


with  pigment;  some  of  the  stroma  cells  also  contain  pigment. 
Diagnosis:  melanoma. 

It  is  difficult  to  believe  this  a  case  of  ordinary  melanotic 
sarcoma  or  melanoma,  inasmuch  as  it  apparently  started  in  the 
lymphatic  gland.  Careful  search  failed  to  reveal  any  primary 
focus  like  a  pigmented  mole  in  any  part  of  the  body.  The  ex- 
tremely rapid  course  of  the  disease  is  also  a  feature  which  I 
have  never  observed  in  any  case  of  melanotic  tumor.  I  have 
just  made  a  study  of  80  cases  of  melanotic  sarcoma  personally 


loo         coley:  neoplasms  of  the  lymphatic  glands 

observed,  and  neither  among  these  cases  nor  in  the  literature 
have  I  found  anything  corresponding  to  such  a  clinical  course. 

Case  LVII.^ — Primary  sarcoma  of  the  cervical  glands  or  tumor 
of  thymus  gland  closely  resembling  an  acute  infectious  disease 

M.  C,  female,  aged  nineteen  years,  entered  St.  Luke's  Hospital 
on  August  7,  1 9 14,  in  the  service  of  Dr.  W.  A.  Downs,  on  account 
of  a  glandular  swelling,  3x2  inches  in  size,  situated  in  the  left 
cervical  region;  there  was  no  redness;  no  fluctuation;  very 
slight  tenderness.  Two  decayed  molar  teeth  with  abscesses 
at  the  roots,  were  found  in  the  left  lower  jaw.  These  were  ex- 
tracted on  August  14,  and  by  September  9  the  mass  of  glands 
had  become  considerably  reduced  in  size.  September  30  the 
reduction  was  much  less  marked,  but  the  swelling  was  smaller 
than  at  time  of  entrance.  October  7,  measurement  of  neck 
13  inches,  October  19,  13I  inches,  October  23,  glands  were 
noticed  for  the  first  time  on  the  right  side  of  the  neck.  December 
30,  the  left  side  of  the  neck  was  normal;  on  the  right  side  the 
glands  were  enlarged  and  had  the  appearance  of  cellulitis. 
January  4,  some  of  the  molar  teeth  on  the  rip^ht  side  were  ex- 
tracted and  the  glands  incised.  She  was  discharged  on  January 
6:  She  was  readmitted  to  St.  Luke's  Hospital  on  January  13. 
On  January  11  there  were  first  noticed  glands  in  the  right  axilla. 
The  tissue  removed  from  the  inflamed  mass  in  the  neck  proved 
on  microscopic  examination  to  be  a  "neoplasm  of  the  round- 
celled  variety;  exact  type  undecided;  either  sarcoma  or  car- 
cinoma; many  mitotic  figures."  January  21,  1915,  the  patient 
was  transferred  to  the  General  Memorial  Hospital.  The  tumor 
rapidly  increased  in  size,  extending  in  all  directions,  upward, 
involving  the  face,  causing  extensive  edema  of  the  lids  of  the  left 
eye  and  the  ear;  downward,  to  the  right  portion  of  the  thorax 
and  laterally  into  both  axillae.  The  skin  was  purple  in  color 
and  ulcerated  over  the  most  prominent  part  of  the  tumor. 
The  patient  ran  a  temperature  ranging  between  100°  and  102.  °5 
from  the  day  she  entered  the  hospital.     She  grew  worse  very 

1  Dr.  Downs  has  kindly  given  me  permission  to  publish  this  case  as  the 
patient  was  on  his  service  in  the  General  Memorial  Hospital. 


coley:  neoplasms  of  the  lymphatic  glands         ioi 

rapidly  and  finally  dyspnea  developed,  causing  death  on  Feb- 
ruary 9. 

Autopsy  report,  made  by  Dr.  Ewing,  showed  the  tumor  to 
involve  the  region  of  the  thymus  gland  and  generally  the  whole 
region  of  the  thyroid,  larynx  and  pharynx  up  to,  if  not  into,  the 
base  of  the  skull,  with  continuous  extension  into  both  axillae 
involving  the  lymphatic  glands  and  encroaching  upon  the  inter- 
costal muscles. 

On  section  one  found  medium-sized  round  and  polyhedral 
and  cylindrical  cells  lying  in  stroma,  chiefly  made  up  of  capillaries, 
covered  by  large  epithelioid  cells  containing  many  lipoid  globules; 
many  cells  resemble  plasma  cells,  others  had  large,  dense  nuclei, 
polymorphism  of  cells  is  the  most  prominent  feature;  no  giant 
cells;  the  large  groups  of  cells  are  surrounded  by  dense  fibrous 
strands  tending  to  become  hyaline. 

Dr.  Ewing's  final  opinion  was  a  primary  malignant  tumor  of 
the  thymus  gland.  He  will  report  the  case  in  fuller  detail. 
The  whole  picture  of  the  disease,  closely  resembles  an  acute 
infection,  starting  in  the  cervical  glands  and  yet  it  was  undoubt- 
edly a  malignant  tumor. 

The  following  cases  are  of  special  interest  and  are  reported 
here  more  fully  than  is  possible  in  the  tables: 

Case  LVIII. — Sarcoma  of  the  neck  and  mediastinum.  Very 
rapid  growth,  causing  death  in  Jour  months. 

G.  W.,  male,  aged  nineteen  years;  student;  always  in  good 
health  until  November  15,  19 13,  when  he  had  a  sudden  severe 
pain  in  both  shoulders;  later  this  became  less  severe  and  inter- 
mittent. December  19,  19 13,  he  noticed  a  short,  dry  cough, 
which  gradually  grew  worse.  Shortly  after  this  he  first  noticed 
enlarged  glands  on  both  sides  of  the  neck,  just  beneath  the 
angle  of  the  jaw.  These  gradually  increased  in  size,  and  in 
addition  the  whole  neck  became  symmetrically  enlarged,  making 
it  necessary  for  the  patient  to  wear  a  No.  18  collar — his  normal 
size  was  No.  15.  The  entire  increase  had  taken  place  within  a 
month's  time.  Marked  dyspnea  developed,  accompanied  by 
rapid  heart  action.     The  patient  was  admitted  to  my  service 


I02         coley:  neoplasms  of  the  lymphatic  glands 

at  the  General  Memorial  Hospital  on  June  20,  1914.  Physical 
examination  at  this  time  showed  a  very  marked  symmetrical 
enlargement  of  the  whole  neck  and  face,  apparently  due  to  ob- 
struction of  the  superior  vena  cava,  dilatation  of  the  superior 
bloodvessels  and  some  cyanosis.  Several  enlarged  glands,  some 
as  large  as  a  hen's  egg,  could  be  felt  on  either  side  of  the  neck, 
deeply  placed,  moderately  firm  in  consistence,  fairly  movable 
non-infiltrating.  Measurement  of  the  neck  at  the  base  (collar 
Une)  on  January  23  was  seventeen  and  three-fourth  inches; 
over  the  thyroid,  sixteen  and  three-fourth  inches.  The  patient 
was  very  weak  and  unable  to  walk;  marked  dyspnea  making 
it  necessary  for  him  to  sleep  sitting  propped  up  in  bed.  Blood 
examination  showed:  Hemoglobin,  85  per  cent.;  white  blood 
cells,  6500;  polynuclears,  73  per  cent.;  mononuclears,  23  per 
cent.;  basophiles,  4  per  cent.  X-ray  examination  showed  a 
tumor  occupying  the  superior  mediastinum,  continuous  with  the 
heart  shadow  and  extending  to  the  root  of  the  neck.  The  patient 
was  immediately  put  upon  small  doses  of  the  toxins;  he  proved 
very  susceptible,  i  to  ^  gr.  causing  a  reaction.  Improvement 
was  noticed  almost  immediately,  as  shown  by  diminution  in  the 
pulse-rate,  lessening  of  the  dyspnea,  marked  decrease  in  the  size 
of  the  neck,  improvement  in  the  cough.  January  26  the  measure- 
ments of  the  neck  had  gone  down  one  and  one-half  inches. 
On  January  29,  one  week  after  admission  to  the  hospital,  measure- 
ment of  the  neck  at  the  base  was  fifteen  and  three-fourth  inches, 
over  the  thyroid  fifteen  inches,  being  a  decrease  of  over  two  inches 
within  a  week.  The  patient  was  given  a:-ray  treatments  in 
addition  to  the  toxins;  his  general  condition  was  markedly 
improved,  he  was  able  to  go  about  and  take  walks  out  of  doors. 
At  the  end  of  two  weeks'  improvement  the  condition  gradually 
became  worse  again,  in  spite  of  continued  treatment  with  the 
toxins  and  a;-rays.  He  left  the  hospital  on  February  18,  1914, 
having  rapidly  grown  worse  daily,  and  died  about  two  weeks 
later. 

Case  LIX. — Lymphosarcoma  of  neck;  clinical  diagnosis  remark- 
ably rapid  development. 


coley:  neoplasms  of  the  lymphatic  glands         103 

Mrs.  H.  P.,  aged  sixty-eight  years;  always  in  good  health 
up  to  July  I,  1 9 13,  except  that  she  had  a  small  epithelioma 
removed  from  the  inner  canthus  of  the  eye  five  years  before  he 
present  disease.  Early  in  July  she  had  a  severe  attack  of 
la  grippe,  with  a  temperature  of  102°  to  103°,  accompanied 
by  cervical  enlargement  on  both  sides,  sore  throat  and  general 
symptoms  of  la  grippe.  She  had  three  similar  attacks  during  the 
month  of  July;  each  time  the  glands  became  rapidly  and  mark- 
edly swollen  with  complete  subsidence  after  the  attack  was  over. 
On  one  occasion  the  doctor  was  summoned  hurriedly  by  the 
patient's  brother  who  stated  that  the  gland  were  twice  the  size 
of  a  hen's  egg.  Five  hours  later,  when  the  doctor  saw  the  patient 
the  glands  had  become  reduced  to  the  size  of  a  hickory  nut. 
A  little  later  the  glands  of  the  left  side  again  became  swollen, 
but,  instead  of  subsiding  as  -hitherto,  they  gradually  increased  in 
size.  In  October  the  increase  became  very  rapid  and  was  ac- 
companied by  infiltration  of  the  surrounding  tissues.  The 
axillary  glands  soon  became  involved,  more  markedly  on  the. 
left  side,  also  the  inguinal  glands.  No  enlargement  of  spleen 
or  liver.  The  patient  failed  rapidly  in  general  condition  and  by 
the  middle  of  December,  1913,  was  confined  to  the  bed.  She 
was  then  seen  by  Dr.  J.  Erdman,  who  made  the  diagnosis  of 
lymphosarcoma.     No  specimen  was  removed. 

I  saw  the  patient  in  consultation  on  December  29,  1913. 
Physical  examination  at  this  time  showed  the  patient  propped 
up  in  hedi  unable  to  lie  down;  her  general  condition  was  ex- 
tremely bad;  pulse  rapid  and  weak;  she  was  unable  to  open  her 
mouth  more  than  a  half-inch.  Examination  showed  the  whole 
left  side  of  the  neck,  from  the  clavicle  to  the  mastoid,  and  the 
anterior  portion  of  the  jaw  nearly  to  the  vertebral  line,  occupied 
by  a  diffuse  tumor,  apparently  involving  all  the  cervical  and 
suproclavicular  glands  with  infiltration  of  the  surrounding  tissues, 
including  the  parotid  and  enormous  dilatation  of  the  superficial 
veins;  paralysis  of  the  muscles  of  the  left  face  and  mouth. 
About  a  week  ago  she  had  had  an  attack  of  almost  complete 
coma;  pulse  130.     Since  this  time  she  has  been  more  or  less 


I04         coley:  neoplasms  of  the  lymphatic  glands 

wandering  mentally,  with  occasional  recurrence  of  slow  respiration 
and  rapid  pulse.  No  treatment  advised.  Prognosis:  only  a 
few  weeks  of  life.     She  died  shortly  afterward. 

Case  LX. — Lymphosarcoma  of  neck — marked  inhibitory  action 
both  under  the  toxin — and  later  x-ray  treatment,  which  proved  only 
temporary  {however).     Unusual  generalization  of  the  disease. 

Miss  M.  L.  A.,  aged  forty  years;  first  noticed  a  tumor  above 
the  clavicle  in  the  spring  of  1898;  this  was  removed.  Shortly 
after  this  a  recurrence  took  place  in  the  right  cervical  region 
which  grew  very  rapidly,  soon  involving  the  axillary  glands  on 
the  same  side.  In  July,  1900,  the  axillary  tumor  was  removed 
by  Dr.  C.  B.  Nancrede,  of  Ann  Arbor. 

The  tumor  in  the  cervical  region  showed  such  extensive 
involvement  of  the  deeper  structures  that  it  was  considered 
entirely  inoperable.  Microscopic  examination  was  made  by 
Dr.  King  of  the  Dartmouth  Medical  School,  who  pronounqed 
it  small  round-celled  sarcoma.  The  patient  was  referred  to  my 
by  Dr.  Nancrede  in  October,  1900.  Physical  examination  at 
this  time  showed  a  large  tumor  in  the  right  cervical  region, 
extending  from  the  clavicle  to  the  mastoid  process  of  the  temporal 
bone.  There  were  some  enlarged  nodules  below  the  clavicle 
and  several  small  tumors  in  the  region  of  the  cicatrix  in  the 
axilla.  The  toxins  were  begun  on  October  i  and  continued, 
with  occasional  intervals  of  rest,  for  six  months.  There  was  a 
decided  decrease  in  the  size  of  the  tumors  and  increase  in  their 
mobility  for  three  months,  when  the  improvement  ceased. 
At  the  end  of  six  months  the  tumors  began  to  increase  in  size 
and  grow  more  rapidly.  In  February,  1902,  the  :r-ray  treatment 
was  begun,  and  at  the  end  of  three  weeks  remarkable  improve- 
ment had  occurred.  The  tumor  mass  in  the  neck  had  decreased 
to  half  its  former  size,  and  by  July  i  there  remained  only  a  small 
nodule  the  size  of  an  almond  in  the  sternomastoid  muscle. 
This  was  removed  for  microscopic  examination.  The  patient 
regained  her  normal  weight.  In  September,  1902,  she  returned 
with  a  local  recurrence  in  the  parotid  region.  Both  groins  were 
filled  with  multiple  tumors  varying  in  size  from  a  pigeon's  to  a 


coley:  neoplasms  of  the  lymphatic  glands         105 

hen's  egg.  In  addition  there  was  an  intra-abdominal  tumor  the 
size  of  a  cocoanut,  apparently  originating  in  the  glands.  The 
x-rsiy  treatment  was  resumed  and  again  the  tumors  disappeared 
in  the  parotid  and  groin  and  the  abdominal  tumor  decreased 
in  size.  The  improvement,  however,  was  only  temporary  and 
in  the  summer  of  1903  the  old  tumors  began  to  increase  again 
in  size  and  many  new  ones  developed  in  all  parts  of  the  body 
intra-abdominally  and  subcutaneously,  causing  death  in  Jan- 
uary, 1904. 

Case  LXI. — Small  round-celled  sarcoma  of  neck.  Held  under 
control  for  ten  years  by  five  operations.  Finally  disappeared  under 
x-ray;  recurred  causing  death  in  two  years. 

G.  F.  H.,  male,  aged  seventy  years;  was  referred  to  me  by 
Dr.  Wm.  T.  Bull,  in  May,  1901,  with  the  following  history: 
About  ten  years  before  he  first  noticed  a  lump  in  the  left  side 
of  the  neck.  One  year  later  the  tumor  was  removed  by  Dr. 
Bull  and  microscopic  examination  proved  it  to  be  a  small  round- 
celled  sarcoma.  The  patient  had  four  subsequent  operations 
within  the  following  seven  years,  one  tumor  was  removed  from 
the  right  side  of  the  neck,  the  others  recurred  locally  in  the 
region  of  the  original  cicatrix  on  the  left  side. 

When  first  seen  by  me  on  May  13,  1901,  physical  examina- 
tion showed  a  tumor  the  size  of  an  orange  occupying  the  left 
mastoid  region,  very  vascular  and  semifluctuating,  another 
glandular  tumor  behind  the  jaw  on  the  right  side,  also  a  growth 
the  size  of  a  small  orange  in  the  right  femoral  region,  and  a  hard, 
freely  movable  glandular  tumor  in  the  right  axilla,  the  size  of 
an  egg.  The  patient  was  treated  with  the  mixed  toxins  and 
received  thirteen  injections  between  May  13  and  June  5,  the 
highest  temperature  obtained  being  102°.  On  June  5  I  tried 
the  externa]  carotid  artery  on  the  left  side.  The  patient  then 
left  the  hospital  for  a  short  rest  and  returned  on  July  16  for 
another  course  of  toxin  treatment,  which  lasted  eleven  days. 
At  first  slight  improvement  followed  the  injections,  but  later  they 
seemed  to  have  little  or  no  influence  upon  the  disease.  I  regarded 
the  case  as  hopeless.    On  December  22,  1901,  the  patient  placed 


io6         coley:  neoplasms  of  the  lymphatic  glands 

himself  under  the  care  of  Dr.  E.  R.  Fiske,  of  Brooklyn,  who 
treated  him  with  the  a:-rays.  A  static  machine  was  used  and 
ten-minute  daily  exposures  were  given  for  the  first  two  weeks 
then  fifteen  minutes  for  the  next  two  weeks  and  twenty  minute- 
exposures  for  the  fifth  and  sixth  week.  The  treatment  was 
followed  by  very  rapid  improvement  in  all  the  tumors.  A  letter 
from  Dr.  Fiske,  January  23,  1903,-  a  little  over  a  year  later 
states  that  "the  patient  has  been  under  constant  observation 
and  there  has  been  no  recurrence.  The  numerous  glandular 
tumors  in  the  axillae  and  groins  have  been  treated  successively 
and  have  yielded  to  the  ic-ray,  some  slowly,  some  very  promptly. 
I  see  him  twice  a  month  and  he  is  in  fine  health." 

The  patient  died  on  September  23,  1903,  less  than  two  years 
after  the  x-ray  treatment  was  begun.  In  a  leHer  from  Dr.  E.  F. 
Sickenberger  it  is  stated  that  the  patient  died  under  symptoms 
of  cerebral  thrombosis.  Whether  this  was  the  result  of  the  dis- 
ease or  not,  can  never  be  determined,  as  no  autopsy  was  made. 
The  pathological  report  of  the  New  York  Hospital,  February 
21,  1892,  reads  as  follows: 

"The  specimen  is  an  oval  tumor  7  x  4.5  inches,  no  capsule; 
on  the  surface  the  voluntary  muscle  fibers  are  seen  invaded  by 
the  tumor  tissue.  Line  of  incision  has  gone  through  the  tumor 
tissue  at  several  points.  Microscopically,  the  tumor  is  a  typical 
round-celled  sarcoma  with  small  amount  of  fibrous  tissue  struma, 
apparently  derived  from  tissues  in  which  the  growth  originated. " 

Examination  October  24,  1893:  "The  specimen  is  a  tumor  the 
size  of  a  hen's  egg  from  the  left  side  of  the  neck,  freely  movable. 
Microscopic  examination  shows  this  growth  to  be  simple 
adenitis." 

The  following  case  is  of  extreme  interest  on  account  of  the 
long  duration  of  the  disease  and  great  size  of  the  tumor: 

Case  LXII. — Lympho-adenomaojneck  twenty-one  years'  duration. 

O.  G.,  male,  aged  fifty-six  years,  occupation,  engraver;  nation- 
ality, Belgian.  Twenty-one  years  ago  he  first  noticed  a  swelling 
on  the  right  side  of  the  neck,  apparently  originating  in  the 
glands.     This  was  soon  followed  by  a  similar  swelling  on  the 


COLEY:   NEOPLASMS    OF   THE    LYMPHATIC    GLANDS 


107 


left  side  of  the  neck.  Six  years  later  the  mass  on  the  right 
side  was  removed,  but  recurred  soon  afterward.  Ten  years  ago 
he  was  subjected  to  a  course  of  x-ray  treatment,  without  any 


Fig.  39. — Case  LXII.       Benign  tumor  of  the  lymphatic  glands  of  twenty-one 
years'  duration.     (Hodgkin's  disease;  one  diagnosis.) 


Fig.  40. — Case  LXII  (neck  case).    Lympho-adenoma,  twenty-one  years'  dura- 
.    tion.     (Ewing.)    Hodgkin's  disease?    (Another  diagnosis). 


io8         coley:  neoplasms  op  the  lymphatic  glands 

improvement.  Five  months  ago  he  was  admitted  to  Roosevelt 
Hospital,  where  some  glands  were  excised  from  the  left  axilla 
and  a  vaccine  made  of  the  material.  Two  injections  were  given 
without  any  improvement. 

Physical  examination  at  the*  time  of  the  patient's  admission 
to  the  General  Memorial  Hospital  on  June  14,  191 5,  shows 
a  large  mass  on  the  left  side  of  the  neck,  firm  in  consistence, 
adherent  to  the  deeper  structures,  not  tender.  The  mass  occupies 
the  whole  of  the  left  side  of  the  neck  and  extends  below  the 
clavicle.  There  is  a  similar  mass,  though  smaller,  on  the  right 
side  of  the  neck  and  another  one  above  the  scapula.  Circum- 
ference of  neck  thirty-one  inches,  on  a  level  of  chin  twenty-three 
inches.  Axillary  glands  palpable  on  both  sides.  The  lungs 
present  masses  of  various  sizes,  which  are  also  shown  in  the 
x-ray  skiagram.  Liver  and  spleen  are  enlarged;  abdominal 
cavity  contains  some  fluid.    Lower  extremities  are  edematous. 

Pathological  report  at  Roosevelt  Hospital:  granuloma  of 
axillary  l5rmph  gland  (probably  Hodgkin's  disease).  Dr.  Ewing's 
diagnosis:  lympho-adenoma. 

Case  LXIII. — Unusual  type  of  neoplasm  of  the  neck.  {Pos- 
sibly similar  to  preceding  case). 

M.  W.  B.,  female,  aged  twenty  years.  Family  history  negative; 
no  trauma;  was  referred  to  me  on  June  6,  19 10,  by  Dr.  J.  L. 
Davison,  of  Toronto,  Canada,  with  the  following  history: 
About  a  year  before,  patient  first  noticed  a  hard,  firmly-fixed, 
lump  in  the  middle  of  the  left  cervical  region,  posterior  to  the 
sternomastoid  muscle.  Very  little  change  in  size  was  noticed 
until  February,  19 10,  when  it  began  to  increase  rapidly.  X-ray 
treatmejnt  was  started  at  this  time  and  continued  three  times 
a  week  for  about  four  months,  during  which  period  the  tumor 
diminished  three-quarters  of  an  inch  in  circumference. 

Physical  examination,  June  6,  1910,  showed  the  whole  left 
cervical  region  occupied  by  a  markedly  protuberant  tumor, 
infiltrating  the  deep  structures  and  extending  from  the  mastoid 
to  the  clavicle;  skin  normal  and  not  attached.  The  tumor 
was  very  hard  in  consistence  and  firmly  fixed.      Under  ether 


coley:  neoplasms  of  the  lymphatic  glands         109 

anesthesia  I  made  an  exploratory  incision  and  removed  a  portion 
of  the  growth  cutting  at  least  one-half  of  an  inch  into  it.  The 
specimen  was  examined  by  Dr.  Ewing,  who  stated  that  he  could 
find  no  evidence  of  malignant  disease. 

The  patient  remained  under  my  care  for  two  months  (June 
and  July,  19 10)  during  which  time  she  received  the  toxins 
regularly  three  or  four  times  a  week,  and  the  doses  were  pushed 
to  the  point  of  producing  fairly  good  reactions.  While  the  tumor 
did  not  increase  any' in  size,  there  was  no  marked  decrease. 
The  toxins  were  continued  by  the  family  physician,  with  oc- 
casional intervals  of  rest,  but  with  little  effect  upon  the  tumor. 
X-ray  and  radium  were  further  tried  but  also  without  effect. 

In  the  summer  of  191 2,  the  patient  again  came  under  my  care, 
at  which  time  she  was  still  in  good  general  condition.  The 
tumor,  which  was  still  firmly  fixed  and  very  hard  in  consistence, 
had  increased  to  two  or  three  times  its  original  size.  The  toxins 
were  again  administered  for  a  number  of  weeks  with  practically 
no  effect  upon  the  growth. 

Since  that  time  she  remained  about  the  same  for  a  year, 
and  then,  without  treatment  and  from  no  apparent  cause,  the 
tumor  began  to  slowly  diminish  in  size  and  her  condition  to 
improve.  At  present.  May,  19 15,  her  physician  writes  that 
she  is  very  well  and  the  tumor  is  not  more  than  one-half  the 
size  it  was  two  years  ago.  In  this  case  it  would  seem  fairly 
certain  that  the  malignancy  of  the  tumor  had  been  modified 
by  the  treatment.  She  had  toxins,  :r-rays  and  radium  during 
a  period  of  about  four  years. 

Case  LXIV. — Small  round-celled  sarcoma  of  the  submaxillary 
region  {carcinoma  of  the  breast  in  the  same  individual). 

Mrs.  M.,  aged  fifty- three  years.  Family  history,  negative; 
was  operated  upon  by  Dr.  E.  G.  Tuttle,  of  New  York,  in  1894, 
for  a  typical  carcinoma  of  the  breast;  diagnosis  confirmed  by 
microscopic  examination.  She  remained  well  until  the  fall 
of  1895,  when  an  enlargement  of  the  left  submaxillary  gland  was 
noticed.  This  continued  to  increase  very  rapidly  in  size  until 
January,  1896,  when  it  had  reached  about  three  inches  in  diameter, 


no         coley:  neoplasms  of  the  lymphatic  glands 

was  fairly  well  fixed  to  the  jaw,  and  considered  inoperable.  The 
patient  was  referred  to  me  by  the  family  physician,  Dr.  R. 
Oliver  Phillips  of  Yonkers,  N.  Y.,  in  January,  1896.  I  believed 
the  tumor  to  be  inoperable,  and  advised  the  use  of  the  mixed 
toxins  of  erysipelas  and  Bacillus  prodigiosus,  which  were  started 
at  once.  After  one  month's  treatment  the  tumor  had  become 
very  much  smaller  and  movable,  and  the  mass  had  decreased 
to  one-third  its   original  size. 


Fig.  41. — Case  XXV  (tonsil  table).  Lymphosarcoma  of  neck  and  tonsil. 
Examination  of  specimen  from  tonsil  called  carcinoma.  Section  is  from  gland 
ofjneck. 

Under  ether  anesthesia  on  March  14,  1896,  I  removed  by 
operation  two  globular  masses,  one  three-quarters  of  an  inch, 
the  other,  one  inch  in  diameter,  from  the  left  submaxillary  region; 
both  were  entirely  encapsulated  and  on  section  showed,  macro- 
scopically,  the  typical  characteristics  of  sarcoma.  Microscopic 
examination,  however,  by  Drs.  E.  K.  Dunham  and  B.  H.  Buxton 
(pathologists  of  the  N.   Y.    Cancer  Hospital)   failed  to  show 


COLEY:    neoplasms    of   the    lymphatic    glands  III 

any  evidence  of  malignancy,  and  a  diagnosis  of  "glandular 
hyperplasia"  was  made.  At  this  time  there  was  no  evidence 
of  any  recurrence  at  the  site  of  the  previous  operation  for  car- 
cinoma of  the  breast,  done  two  years  before.  However,  in  June, 
1896,  three  months  later,  a  well-marked  local  and  axillary 
recurrence  took  place  at  the  site  of  the  former  breast  operation. 
The  disease  progressed  rapidly  and  in  July,  1896,  I  removed 


Fig.  42. — Lymphosarcoma  of  supraclavicular  and  retroperitoneal  glands; 
very  rapid  progress.  Patient  died  in  three  months.  Primary  in  retroperi- 
toneal probably. 

the  entire  diseased  area,  together  with  both  pectoral  muscles. 
The  patient  made  a  prompt  recovery.  Microscopic  examination 
of  this  tumor  showed  it  to  be  a  typical  scirrhous  carcinoma. 
A  few  weeks  later  a  recurrence  took  place  at  the  site  of  my 
operation  in  the  submaxillary  region.  The  tumor  grew  with 
great  rapidity  and  was  no  longer  controlled  by  the  toxins.  In 
September,  1896,  I  performed  another  operation  removing  an 
encapsulated  tumor,  the  size  of  a  small  egg,  which  presented 


112         coley:  neoplasms  of  the  lymphatic  glands 

exactly  the  same  characteristics  as  the  first.  In  view  of  the 
macroscopic  appearance  and  the  prompt  recurrence,  I  felt 
certain  that  the  tumors  in  this  region  were  malignant  (not  hyper- 
plasia), and  asked  for  a  very  careful  report.  The  specimens 
were  again  examined  by  Drs.  Dunham  and  Buxton,  but  a  large 
number  of  sections  were  made  before  any  evidence  of  sarcoma 
was  discovered.  Finally,  areas  were  found  that  showed  typical 
round-celled  sarcoma. 

One  month  later  a  second  recurrence  took  place.  The  tumor 
grew  with  great  rapidity  involving  and  infiltrating  the  tissue 
on  both  sides  of  the  neck.  The  patient  died  of  exhaustion  on 
March  i8,  1897,  five  months  later.  A  very  slight  skin  recurrence 
in  the  region  of  the  breast  tumor  was  observed  before  death. 

This  case  is  interesting  from  the  fact  that,  in  the  first  place, 
it  is  one  of  the  rare  cases  of  sarcoma  associated  with  carcinoma 
in  the  same  individual,  and,  in  the  second  place,  it  emphasizes 
the  fact  that  in  certain  cases  strong  clinical  evidence  in  favor 
of  malignancy,  should  outweigh  negative  microscopic  evidence 
against  malignancy. 

Reports  of  a  few  of  the  more  interesting  cases  of  sarcoma  of 
the  lymphatic  glands  successfully  treated  by  other  men,  are 
included. 

Case  I. — Spindle-celled  sarcoma  of  neck  just  above  the  clavicle, 
recurrent  in  thoracic  wall,  incomplete  operation  followed  by  toxin 
treatment.  Entire  disappearance,  patient  well  for  eight  years, 
when  she  died  of  an  acute  pulmonary  condition.  {Case  of  Dr. 
Joseph  Grindon,   St.   Louis,   Mo.) 

Mrs.  B.,  aged  fifty  years,  mother  of  a  large  family,  consulted 
Dr.  Grindon  in  April,  1897,  for  a  firm,  rounded,  painless  mass, 
about  2  cm.  in  diameter,  immediately  above  the  left  clavicle 
and  just  behind  the  sternomastoid  insertion.  It  had  been  noticed 
only  a  few  days.  There  was  no  history  or  evidence  of  lues  or 
tuberculosis.  A  diagnosis  of  malignancy  was  made  and  the  case 
referred  to  Dr.  P.  Y.  Tupper  for  operation.  He  agreed  in  the 
diagnosis  and  operated  two  days  later.  On  dissecting  down, 
the  growth  was  found  to  extend  into  the  thorax  behind  the  first 


coley:  neoplasms  of  the  lymphatic  glands         113 

and  second  ribs  and  possibly  much  deeper,  so  that  complete 
extirpation,  if  at  all  possible,  would  have  necessitated  disarticula- 
tion of  the  clavicle  and  ligation  of  the  subclavian  vessels.  As 
much  of  the  mass  as  could  be  reached  without  disturbing  the 
clavicle  was  excised  and  the  wound  closed.  The  growth  was 
submitted  to  Dr.  Kodis  pathologist  to  the  medical  department 
of  Washington  Universtiy,  who  pronounced  it  a  spindle-celled 
sarcoma.  The  incision  promptly  healed,  but  a  few  days  later 
the  skin  thinned  and  assumed  a  bluish  look  and  in  a  few  more 
days  broke  down.  The  mass  rapidly  regained  its  former  size 
soon  exceeded  it  and  continued  to  increase  in  size.  The  patient 
began  to  lose  flesh.  She  became  anemic  and  so  weak  that  she 
no  longer  could  leave  per  bed. 

A  supply  of  Dr.  Coley's  mixed  toxins  was  obtained  from  the 
Loomis  Laboratory,  and  an  injection  given  in  the  back  every 
third  day,  beginning  with  one-half  minim  and  working  up  to 
eight  minims.  She  received  in  all  fifty-eight  injections  between 
the  middle  of  April  and  the  middle  of  October.  Local  and  general 
reactions  were  severe  almost  from  the  first,  consisting  of  a 
wide  zone  of  erysipelas-like  inflammation,  spreading  from  the 
site  of  injection,  with  constitutional  disturbances  coming  on 
after  about  two  hours,  conisting  of  chill,  followed  by  fever, 
vomiting,  headache  and,  on  one  or  two  occasions,  mild  delirium. 
In  spite  of  all  this  she  soon  began  to  gain  in  weight,  strength 
and  general  appearance.  Meanwhile  the  growth  rapidly  sub- 
sided and  finally  disappeared.  By  September  the  patient  was 
apparently  completely  well.  She  received  no  other  treatment 
than  the  toxins. 

In  February,  1898,  several  growths  appeared  on  the  right 
thoracic  wall,  just  below  the  axilla.  Four  injections  of  the  mixed 
toxins  were  given  in  February  and  two  in  March,  without 
visible  effect.  In  April  the  case  was  referred  for  operation 
to  Dr.  V.  P.  Blair  (Dr.  Tupper  being  away).  Several  masses  from 
2  to  3  cm.  in  diameter  were  removed  and  submitted  to  Dr.  Carl 
Fish  for  microscopic  examination.  His  report  was  spindle- 
celled  sarcoma.     Twenty-two  injections  in  gradually  increasing 


114         coley:  neoplasms  of  the  lymphatic  glands 

doses  were  given  during  May,  June,  and  July.  The  wound  healed 
and  the  patient  remained  free  from  recurrence.  She  died  eight 
years  later  of  an  acute  pulmonary  condition. 

Case  II. — Small  round-celled  sarcoma  of  the  glands  oj  the  groin. 
(Case  of  Dr.  Alfred  Jacoby,  of  New  Orleans,  La.) 

W.  S.,  male,  aged  fifty-eight  years;  family  history  good.  No 
history  of  injury,  except  a  strain  in  the  region  of  the  groin,  in 
March,  191 2.  Six  days  later  he  noticed  a  slight  swelling  of  the 
glands  n  the  left  inguinal  region.  This  increased  steadily  in 
size  more,  rapidly  during  the  last  four  weeks,  and  on  April  25, 
191 2,  or  six  weeks  after  the  strain,  he  entered  the  Charity 
Hospital  in  New  Orleans,  where  Dr.  F.  W.  Parham  performed  an 
operation,  which,  in  his  opinion,  was  incomplete.  The  flap 
sloughed  and  a  large  granulating  surface  was  left.  The  toxins 
were  begun  and  carried  out  under  my  direction  by  Dr.  A.  Jacoby, 
of  New  Orleans,  on  May  21,  1912,  the  initial  dose  being  0.5 
minim,  which  was  increased  daily  up  to  a  point  of  getting  a  good 
reaction.  The  wound  healed  rapidly  under  the  injections  and  the 
patient  was  entirely  well  July  13,  1912,  although  the  injections 
were  continued  until  July  30.  The  patient  was  in  good  health 
when  last  seen  by  Dr.  Jacoby,  in  June,  1915.  The  pathological 
diagnosis  in  this  case  was  small  round-celled  sarcoma. 

Case  III. — Recurrent  small  round-celled  sarcoma  of  neck; 
mixed  toxins  used  after  second  operation;  patient  well  eight  years. 
(Case  of  Dr.  J.  H.  Glass,  of  Utica,  N.  Y.) 

M.  S.,  male,  aged  nineteen  years.  In  the  spring  of  1905, 
the  patient  first  noticed  a  small  swelling  in  the  submental  region 
which  remained  about  the  same  in  size  until  the  spring  of  1906, 
when  it  began  to  increase  rapidly.  The  first  operation  was  done 
on  February  28,  1906,  by  Dr.  D.  M.  Marshall,  of  Toledo,  O. 
A  tumor  about  two  inches  in  diameter  was  removed  from  the 
median  line  between  symphysis  and  hyoid  bone.  No  micro- 
scopic examination  was  made.  Within  a  week  after  the  opera- 
tion, a  recurrence  took  place,  which  increased  rapidly  in  size. 
On  March  13,  1906,  the  patient  entered  the  Faxton  Hospital 
of  Utica,  service  of  Dr.  J.  H.  Glass,  who  stated  that  he  found 


coley:  neoplasms  of  the  lymphatic  glands  115 

the  tumor  to  extend  along  both  sides  of  the  inferior  maxilla, 
involving  the  lymph  glands.  The  recurrent  tumor  together  with 
both  sublingual  glands  was  removed.  The  report  of  the  micro- 
scopic examination  made  by  Dr.  Wm.  Smith  Nelson  stated 
that  the  picture  was  a  perfect  one  of  small  round-celled  sarcoma. 
The  mixed  toxins  of  erysipelas  and  Bacillus  prodigiosus  were 
started  almost  immediately  after  the  operation  in  the  hope  of 
preventing  a  recurrence. 

A  letter  from  Dr.  Glass,  dated  February  11,  1914,  stated: 
"The  patient  is  alive  and  in  good  health  at  present,  eight  years 
after  the  treatment." 

Case  IV. — Lymphosarcoma  of  neck. 

The  following  case  was  treated  by  Dr.  George  P.  Miiller,  of 
Philadelphia,  and  partially  reported  in  the  Transactions  of  the 
Philadelphia  Surgical  Society  meeting,  November  10,  1909, 
Annals  of  Surgery,  February,  1910.  The  patient,  male,  aged 
twenty-eight  years,  was  admitted  to  Dr.  Frazier's  ward  in  the 
University  Hospital  and  operated  upon  by  Dr.  Miiller  for  a 
large  lymphosarcoma  of  the  neck.  This  was  dissected  out  as 
carefully  as  possible,  but  within  a  month  a  local  recurrence  took 
place  along  the  trapezius,  which  was  also  removed.  The  patient 
was  immediately  put  upon  the  mixed  toxins  and  remained 
well  for  four  years,  as  per  Dr.  Miiller's  letter  of  April  21,  191 1. 
One  month  thereafter  a  recurrence  was  noticed,  the  patient 
lost  thirty  pounds  in  weight  and  his  general  health  deteriorated 
very  rapidly.  In  spite  of  the  resumption  of  the  toxin  treatment 
he  died  within  a  year  after  the  onset  of  the  recurrence. 

Case  V. — Mixed-celled  sarcoma  of  neck. 

A.  G.  W.,  male,  treated  under  my  direction  by  Dr.  O.  S.  C. 
Davies,  of  Augusta,  Me.  The  patient  had  first  noticed  an 
enlargement  just  back  of  the  angle  of  the  jaw  in  July,  1900. 
On  February  21,  1901,  the  growth  which  had  attained  the  size 
of  a  small  hen's  egg,  was  removed  as  thoroughly  as  possible 
by  Dr.  Davies  and  examined  by  Prof.  F.  N.  Whittier,  of  Bowdoin 
College,  who  pronounced  it  sarcoma.  He  stated,  "The  cells 
seem  to  be  a  mixture  of  large,  small  and  spindle."     On  April 


ii6        coley:  neoplasms  of  the  lymphatic  glands 

30,  1901,  two  months  after  the  operation,  the  tumor,  having 
returned,  was  half  as  large  as  it  was  at  the  time  of  operation 
and  involved  the  anterior  border  of  the  sternocleidomastoid 
muscle  and  the  deeper  structures. 

On  this  date  Dr.  Davies  consulted  me  about  the  case,  and  I 
advised  a  trial  with  the  mixed  toxins,  which  were  begun  at  once 
and  continued  three  times  a  week  until  May  25.  The  treatment 
was  then  discontinued  for  a  month,  resumed  and  continued 
until  August  14,  at  which  time  the  tumor  had  entirely  disappeared. 
I  received  a  number  of  communications  from  Dr.  Davies  re- 
garding the  later  history  of  the  case.  One  letter,  dated  December 
6,  1905,  states,  "The  patient  is  still  in  good  health." 

The  patient  died  in  November,  191 2,  eleven  years  after  the 
disappearance  of  the  tumor,  of  what  was  supposed  to  have  been 
pulmonary  tuberculosis.  The  remaining  cases  successfully  treated 
by  other  surgeons  will  be  found  in  tabular  form  at  end  of  paper. 

The  following  tables  cover  168  cases  of  primary  neoplasms 
of  the  lymphatic  glands,  including  Hodgkin's  disease  personally 
observed  within  the  last  twenty-four  years: 

With  regard  to  locality,  the  cases  are  distributed  as  follows: 

77  cases  of  sarcoma  of  the  neck.  » 

25  cases  of  sarcoma  of  the  tonsil  and  neck. 
10  cases  of  sarcoma  of  the  retroperitoneal   and  mesenteric 
glands. 

17  cases  of  sarcoma  of  the  inguinal  glands. 

18  neoplasms  of  the  axillary  glands  (16  sarcomas  2  car- 
cinomas,) . 

21  cases  of  Hodgkin's  disease. 
I  case  of  sarcoma  of  the  mediastinal  glands. 

As  regards  the  relative  frequency  of  lymphosarcoma  in  the 
sexes,  my  tables  show  a  great  preponderance  of  males  over 
females  throughout  the  entire  series,  except  in  the  mesenteric 
gland  cases,  in  which  the  proportion  is  equal,  e.  g.: 

Retroperitoneal  and  mesenteric  glands,  10  cases  (5  males  and 
5  females). 


coley:  neoplasms  of  the  lymphatic  glands         117 

Axillary  glands,  18  cases  (10  males  and  8  females). 
Inguinal  glands,  17  cases  (12  males  and  5  females). 
Neck,  77  cases  (54  males  and  23  females). 
Hodgkin's  disease,  21  cases  (16  males  and  5  females). 
Tonsil  and  neck,  24  cases  (20  males  and  4  females). 

The  duration  of  life  in  the  fatal  cases,  so  far  as  definite  data 
are  available,  may  be  of  some  interest: 

2  died  within  ten  days. 

12  died  within  a  few  weeks. 

20  died  within  less  than  six  months. 

13  died  within  six  months  to  one  year. 
II  died  within  one  to  two  years. 

5  died  over  two  years  after  the  onset  of  the  disease. 

A  summary  of  the  cases  personally  observed  shows  that  26 
of  the  patients  have  been  successfully  treated — that  is,  the 
tumors  (inoperable)  entirely  disappeared — with  the  mixed 
toxins  of  erysipelas  and  Bacillus  prodigiosus,  and  have  remained 
well  from  one  to  twenty-two  years.  Nineteen  patients  remained, 
well  from  three  to  twenty-two  years. 

Of  77  cases  of  sarcoma  of  neck,  8  have  remained  well  from 
two  to  fourteen  years. 

I  round-celled  sarcoma  of  neck,  well  two  years. 

I  sarcoma  of  neck,  well  two  years. 

I  adenocarcinoma  of  neck,  well  three  years  and  then  re- 
curred. 

I  round-celled  sarcoma  of  neck,  well  four  years  (the  primary 
tumor  was  called  sarcoma). 

I  round-celled  sarcoma  of  neck,  well  six  years. 
I  round-celled  sarcoma  of  neck,  well  six  and  one-half  years. 
I  small  round-celled  sarcoma  of  neck,  well  thirteen  years. 
I  round-celled  sarcoma  of  neck,  well  fourteen  years. 

Of  24  cases  of  sarcoma  of  tonsil  and  neck,  five  have  remained 
well  from  one  and  one-half  to  nine  and  one-half  years. 


ii8         coley:  neoplasms  of  the  lymphatic  glands 

I  round-celled  sarcoma,  well  one  and  one-half  years. 

I  round-celled  sarcoma,  well  four  and  one-half  years. 

I   round-celled  sarcoma,   well   six  years. 

I  spindle-celled  sarcoma,  well  eight  years. 

I  round-celled  sarcoma,  well  nine  and  one-half  years. 

Of  lo  cases  of  sarcoma  of  the  mesenteric  and  retroperitoneal 
glands,  4  have  remained  well  from  one  to  twelve  years. 

I  round-celled  sarcoma,  well  one  year. 
I  round-celled  sarcoma,  well  two  years. 
I    spindle-celled   sarcoma,   well    two  years. 
I  spindle-celled  sarcoma,  well  twelve  years. 

Of  17  cases  of  sarcoma  of  inguinal  glands,  3  have  remained 
well  from  four  to  seven  years. 

I  sarcoma,  well  four  and  a  half  years. 

I  sarcoma,  well  four  years. 

I  small  round-celled  sarcoma,  well  seven  years. 

Of  18  cases  of  neoplasm  primary  in  the  axillary  glands,  4  have 
remained  well  from  three  to  nine  years. 

I  round-celled  sarcoma,  well  three  years. 
I    round-celled   sarcoma,    well    four   years. 
I   lymphosarcoma,   well    four   years. 
I   l3niiphosarcoma,   well  nine  years. 

I  case  of  sarcoma  of  mediastinal  glands  has  remained  well 
six  years. 

Of  21  cases  of  Hodgkin's  disease  i  remained  well  for  seven 
months  after  complete  disappearance  of  the  disease  under  five 
weeks'  toxin  treatment.  The  patient  refused  further  treatment 
and  died  of  a  recurrence  one  year  later. 

In  the  list  of  cases  of  other  men,  (treated  under  my  direction) 
one  Hodgkin's  case  recovered  and  remains  well  at  present, 
seven  years  later. 


coley:  neoplasms  of  the  lymphatic  glands         119 
recurrence  after  apparent  cure  with  the  mixed 

TOXINS 

In  a  certain  number  of  cases  in  which  the  tumor  or  tumors 
had  entirely  disappeared  under  the  toxin  treatment  and  the 
patients  were  apparently  cured,  the  disease  recurred  at  varying 
intervals  from  six  monhts  to  six  years.  A  study  of  these  cases 
may  be  of  some  interest: 

In  one  case,  after  a  very  large  and  rapidly  growing  primary 
neoplasm  of  the  lymphatic  glands  had  apparently  entirely 
disappeared,  the  disease  returned  and  progressed  rapidly  when 
the  dose  of  the  toxins  was  diminished,  but  began  to  decrease 
again  and  finally  disappear  under  larger  doses  of  the  toxins. 
The  patient  is  now  well  two  years  and  a  half. 

In  another  case,  a  round-celled  sarcoma  of  the  tonsil  with 
extensive  metastases  in  the  neck,  the  tumors  entirely  disappeared 
under  six  months'  treatment  with  the  mixed  toxins;  one  and 
one-half  years  later  a  recurrence  took  place  in  the  glands  of  the 
neck,  which  proved  fatal  within  six  months. 

In  a  third  case,  a  round-celled  sarcoma  of  the  tonsil  and  glands 
of  the  neck,  the  tumors  having  almost  entirely  disappeared 
under  five  weeks'  toxin  treatment,  began  to  increase  in  size 
again  when  the  dose  was  reduced.  Under  increased  doses  the 
tumors  completely  disappeared.  Six  months  later  a  recurrence 
took  place  which  proved  fatal  within  a  year. 

In  another  case  still,  a  round-celled  sarcoma  of  tonsil  with 
extensive  metastases  in  the  neck,  the  disease  entirely  disap- 
peared under  eight  weeks'  toxin  treatment.  The  patient  remained 
well  for  six  years,  when  a  recurrence  or  a  new  tumor  developed 
in  the  opposite  tonsil;  this  tumor  recurred  very  quickly  after 
two  operations  and  caused  death  within  four  months. 

In  one  case,  an  intra-abdominal  sarcoma  primary  in  the 
mesenteric  glands  and  small  intestine,  the  disease  entirely  dis- 
appeared under  four  months'  toxin  treatment,  then  recurred 
one  and  one-half  years  later  and  proved  fatal  within  six 
months. 


I20         coley:  neoplasms  of  the  lymphatic  glands 

In  one  case,  an  alveolar  sarcoma,  primary  in  the  glands  of 
the  neck,  the  disease  almost  completely  disappeared  under 
four  months'  toxin  treatment;  the  patient  remained  well  for 
three  years,  when  a  recurrence  took  place;  incomplete  removal 
followed  by  the  toxins  and  :r-rays;  patient  well  at  present, 
six  months  later.  In  this  case  the  tumor  was  pronounced  adeno- 
carcinoma by  Dr.  Ewing.^ 

Small  round-celled  sarcoma  of  the  inguinal  glands;  complete 
disappearance  under  the  toxins;  recurrence,  which  again  yielded 
to  the  toxins ;  the  patient  is  well  at  present,  seven  years  later. 

In  a  recent  case  of  recurrent  inoperable  sarcoma  of  the  tonsil 
and  neck,  the  tumors  decreased  to  one-fourth  their  original 
size  under  six  weeks'  toxin  treatment.  Then  the  improvement 
ceased  and  the  remaining  tumor  was  removed  by  operation 
followed  by  toxin  treatment  which  was  kept  up  for  about  two 
months.  The  patient  then  left  for  a  two  weeks'  vacation. 
Examination  upon  his  return  showed  a  recurrent  tumor  one  inch 
in  diameter  at  the  site  of  the  incision.  He  was  again  put  upon 
the  toxins  and  while  the  disease  was  apparently  held  in  check, 
there  was  no  noticeable  decrease  in  the  size  of  the  tumor.  Under 
the  combined  toxin  and  radium  treatment  which  has  been  con- 
tinued up  to  the  present  time,  the  tumor  rapidly  decreased 
in  size  and  there  is  now  scarcely  more  than  an  indurated  edge 
at  the  site  of  the  tumor.  September  21,  1915:  Local  recurrence 
with  cervical  and  mediastinal  metastasis  have  developed  and 
general  condition  is  rapidly  growing  worse  in  spite  of  continued 
toxin,  x-ray  and  radium  treatment.  For  later  notes  see  Case 
No.  XVIII. 

In  connection  with  these  recurrences,  a  brief  reference  to  my 
first  case  treated  with  the  living  cultures  of  streptococcus  of 
erysipelas  in  1891,  may  be  of  interest:  Inoperable  spindle-celled 
sarcoma  of  the  tonsil  with  extensive  metastases  on  the  neck; 
both  primary  and  secondary  tumors  almost  completely  dis- 
appeared following  an  attack  of  erysipelas  produced  by  inocula- 
tion in  October,   1891.     The  patient  remained  well  for  eight 

'  December  i,  19 15  there  is  now  evidience  of  mediastinal  involvement. 


COLEY:   neoplasms    of   the    lymphatic    glands  121 

years  and  then  had  a  local  recurrence  which  proved  fatal  within 
a  year. 

The  most  important  lesson  to  be  learned  from  a  study  of  these 
recurrent  cases  I  believe  is  that  in  many  cases  the  treatment  was 
not  kept  up  sufficiently  long. 

I  am  convinced  that  it  is  better  to  continue  the  treatment 
longer  than  may  be  absolutely  necessary  in  a  certain  number  of 
cases,  rather  than  run  the  risk  of  a  recurrence  by  too  short  a 
course  of  treatment  in  certain  other  cases. 

In  cases  in  which  the  toxins  fail  to  control  the  disease  I  believe 
it  advisable  to  use  x-rays  or  radium  or  both  in  conjunction  with 
the  toxins. 

A  summary  of  the  cases,  36  in  number  successfully  treated 
with  the  mixed  toxins  by  other  men,  shows  the  following: 

6  cases  of  sarcoma  of  the  mesentery. 

6  cases  of  sarcoma  of  the  retroperitoneal  glands. 
17  cases  of  sarcoma  of  the  neck. 

3  cases  of  sarcoma  of  the  tonsil  and  neck. 
2  cases  of  sarcoma  of  the  inguinal  glands. 
I  case  of  Hodgkin's  disease  (well  seven  years). 
I  case  of  multiple  sarcoma. 

Of  these,  30  remained  well  from  one  to  seventeen  years. 

7  remained  well  from  twelve  to  seventeen  years. 
21  remained  well  from  three  to  seventeen  years. 

II  remained  well  from  five  to  seventeen  years. 

Most  of  these  cases  appear  in  tabulated  form  in  my  paper 
read  before  the  third  International  Conference  of  Cancer 
Research,  Brussels,  August  i  to  5,   1913. 


122 


coley:  neoplasms  oe  the  lymphatic  glands 


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191S,      7      years 
later. 

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ance   of   tumor; 
doses    again    cut 
down;     recur- 
rence;    toxins 
showed  less  and 
less  effect;  rapid 
growth;      death, 
Feb.      7,      1912; 
complete     au- 
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COLUMBIA  UNIVERSITY  LIBRARIES 

This  book  is  due  on  the  date  indicated  below,  or  at  the 
expiration  of  a  definite  period  after  the  date  of  borrowing,  as 
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ment  with  the  Librarian  in  charge.       '^           ^ — ^ 

DATE  BORROWED 

DATE  DUE 

DATE  BORROWED 

DATE  DUE 

m\!(  2  r 

f 

^""^^r         ,. 

nr^T     5  IS 

'i !!? 

-    '"  ^<^^ 

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Coley 

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